Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule.

BACKGROUND: The challenge of delabeling amoxicillin allergy is an important issue for patients and clinicians, especially when anaphylaxis is reported. A recent study has proposed a clinical decision rule, PEN-FAST, to identify low-risk penicillin allergies. OBJECTIVE: To validate the PEN-FAST clinical decision rule in a population with high risk of suspected immediate amoxicillin allergy and to identify clinical predictive factors of amoxicillin immediate hypersensitivity. METHODS: We retrospectively analyzed medical records of patients with a suspected immediate amoxicillin allergy who carried out an allergologic evaluation by a specialist in the Allergy Unit of Strasbourg University Hospital from 2015 to 2020. RESULTS: A total of 142 adult patients (88 women [62.0%]; median age, 52 [interquartile range, 40.3-62.0] years) were analyzed. Most of them reported anaphylaxis (68.8%). Internal validation of PEN-FAST score revealed a good discrimination with area under the curve of 0.86 (95% confidence interval, 0.79-0.92). A cutoff of less than 3 points for PEN-FAST was used to classify 29 from 142 patients at low risk of allergy, of whom only 2 (6.9%) received positive results of allergy testing. The negative predictive value for successful delabeling was 0.93 (95% confidence interval, 0.77-0.99). Predictive clinical features for immediate amoxicillin hypersensitivity were time since reaction (P < .001), time elapsed between drug intake and first symptom (P < .001), severity grade reaction (P < .001), and treatment or hospitalization required (P < .001). CONCLUSION: PEN-FAST has been validated to identify low-risk penicillin allergies in our European cohort of patients mainly reporting anaphylaxis. This is the first reported external validation of a penicillin allergy clinical decision rule internationally.

Hydrolyzed Rice Protein-Based Formulas, a Vegetal Alternative in Cow's Milk Allergy.

Formulas adapted to infant feeding, although most of the time made from cow's milk proteins, can be made from hydrolyzed rice protein but they must be classified as "formulas for specific medical needs", according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow's milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow's milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.

Immediate Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study.

BACKGROUND: Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors. METHODS: Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT. FINDINGS: Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p < 0.0001). Cardiovascular signs were strongly associated with allergy. Non-allergic IH was observed in 152 patients (62%) (ICM:134; GBCM:18). Severity grade was lower (p < 0.0001) and reaction delay longer (11.6 vs 5.6 min; p < 0.001). Potentially allergic IH was diagnosed in 42 patients (17.1%) (ICM:34; GBCM:8). The delay, severity grade, and mediator release were intermediate between the two other groups. INTERPRETATION: Allergic IH accounted for < 10% of cutaneous reactions, and > 50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria.

Safety of a New Amino Acid Formula in Infants Allergic to Cow's Milk and Intolerant to Hydrolysates.

OBJECTIVES: Amino acid-based formulas (AAFs) are recommended for children with cow's-milk allergy (CMA) failing to respond to extensively hydrolysed formulas (eHFs). We evaluated the effects of a new thickened AAF (TAAF, Novalac), containing a pectin-based thickener, and a reference AAF (RAAF, Neocate) on allergy symptoms and safety, through blood biochemistry analysis and growth. METHODS: Infants (ages < 18 months) with CMA symptoms failing to respond to eHFs were randomised in a double-blind manner to receive TAAF or RAAF for 3 months. All of the infants were then fed TAAF for 3 additional months. Paediatric visits occurred at 1, 3, and 6 months. Blood samples were collected at inclusion and 3 months. RESULTS: Results at 1 month were previously described. The 75 infants with proven CMA and eHF intolerance tolerated their allocated formula. At 3 months, the dominant allergic symptom had disappeared in 76.2% of the infants with TAAF and in 51.5% of the infants with RAAF (P = 0.026). The Scoring Atopic Dermatitis Index significantly improved more with TAAF than with RAAF (-27.3 ±â€Š2.3 vs -20.8 ±â€Š2.2, P = 0.048). Of the infants, 92.9% had normal stools (soft or formed consistency) with TAAF vs 75.8% with RAAF (P = 0.051). More infants in TAAF group had better quality of nighttime sleep (P = 0.036) and low frequency of irritability signs (P < 0.001). With both formulas, all of the biochemical parameters were within normal ranges. There were no differences between the 2 groups in any of the anthropometric z scores. CONCLUSIONS: The new TAAF was tolerated by all of the infants with CMA and intolerance to eHFs. Anthropometric and clinical data showed that both formulas were safe.

A thickened amino-acid formula in infants with cow's milk allergy failing to respond to protein hydrolysate formulas: a randomized double-blind trial.

INTRODUCTION: Amino-acid-based formulas (AAFs) are recommended for children with cow's milk protein allergy (CMPA) failing to respond to extensively hydrolyzed formulas (eHFs). OBJECTIVE: This study aimed to assess the tolerance/hypoallergenicity and efficacy of a thickened AAF (TAAF) in these infants. METHODS: This multicenter, double-blind, randomized controlled trial (NCT01940068) compared 3-month feeding with a pectin-based TAAF (Novalac(®), United Pharmaceuticals, Paris, France) and a commercially available "reference" AAF (RAAF; Neocate(®), Nutricia, Germany) in infants aged <18 months with CMPA and persistent allergy symptoms with eHF feeding. Reported here are the results of an interim analysis after 1 month of feeding. RESULTS: Of the 86 infants randomized, CMPA with eHF intolerance was confirmed in 75 infants; all of them tolerated the allocated AAFs. The major allergic symptom disappeared within 1 month in 61.9 and 51.5 % and regurgitations disappeared in 66.7 and 42.3 % of infants who received TAAF and RAAF, respectively. Infants had significantly more normal stools (soft or formed consistency) with the TAAF (90.5 vs. 66.7 %; p = 0.011). From baseline, daily family life significantly improved with both AAFs: crying time decreased by 97.3 (p < 0.001) and 28.6 min (p = 0.014) and sleeping time increased by 64.6 (p = 0.009) and 29.0 min with TAAF and RAAF, respectively. At day 30, weight and body mass index z-score gains were 0.1 and 0.2 with TAAF and 0.2 and 0.0 with RAAF. CONCLUSION: Both AAFs were well tolerated by infants with CMPA and eHF intolerance and ensured appropriate growth, with the TAAF providing additional comfort.