Table 3.
Studies on oral food challenge (OFC) protocol and development of severe symptoms in children with FPIES, according to the food. CMP: cow’s milk protein; ICU: intensive care unit; IVF: intravenous fluid.
| Authors | Study population (age) | Suspected food | OFC protocol -Dosage | Latency time to symptoms onset | PositiveOFCN. (%) | Severe Symptoms |
|---|---|---|---|---|---|---|
| Katz 2011 (2) | Less than 6 months | Cow's milk | Five consecutive doses: 5mL (150 mg of CMP), 20mL (600 mg of CMP), 30 mL (900 mg of CMP), 60 mL (1.8 g of CMP), 120 mL (3.6 g of CMP), and finally a maximum dose of up to 150 mL (4.50 g of CMP) depending on the tolerance of the infant to drink such a volume. After the 60-mL dose and thereafter, the time interval between the doses was 45 minutes | Range time: 60-315 min from the first dose (mean time: 221.2 ± 71.5 SD min)Mean time: 120 ± 55.2 SD min from the last dose | 28 (100) | IVF: 0 Steroids: 0 Ondansetron: 0 Hypotension = 0 Admission to ICU = 0 Severe reactions* = - |
| Infante 2019 (77) | Two different methods: Method 1 group: 36 months (IQR = 25-48), Method 2 group: 60 months (IQR = 29.5-84) | Fish | Method 1 consisted in giving several doses over 30 min during the same day. Initially, a dose equal to 1/8 (12.5%) of the serving size per age was given, then a 1/4 (25%), 1/2 (50%), and finally the remaining of the whole meal Method 2. The first day a unique dose of 25% of the serving size per age was given followed by a 4-h clinical observation. If the children remained asymptomatic for the next 24 h, 48 h later a 50% of the serving size per age was served followed by a 4-h observation, and if they still remained asymptomatic for the next 24 h, we gave them a normal serving size per age on the third non-consecutive day | Method 1, except in two of them, the symptoms started after the complete serving size per age was given Method 2, only in 6 (18.75%) the symptoms appeared after the whole meal was eaten. | 43 (57.3) | Method 1: Severe reactions: 17 (39.5%) Admission to ED or hospitalized: 18(42%) Method 2:Severe reactions: 4 (12.5%) Admission to ED orhospitalized: 8 (25%) |
| Hwang 2008 (74) | aged 36 days, (SD 14) range 13-58 | Cow's milk, soy | A single dose consisting of 0.15 g of CMP/kg body weight (one spoon of formula mixed with 20 ml of water). | The symptoms began not before than 1,1 from the single dose | 27 (37.5) | IVF = -Hypotension = 3 (11.1) Admission to ICU = -Cyanosis: 6 (22%)Lethargy: 27 (100)Projectile vomiting 27 (100) Diarrhoea 9 (33) Steroids: -Severe reactions = - |
| Powell 1978 (62) | 5.5 months (average age) | Cow's milk, soy | A single serving dose of cow's or soy milk (100 ml) | Only in one of them onset of symptoms at at lh, the remaining at least 1,5 h after the single dose | 14 (77.8) | IVF = -Vomiting = 10 (71.4) Diarrhoea =14 (100) Hypotension = 0 ** Admission to ICU = 0 ** Severe reactions* = 0 |
| Sicherer 1998 (47) | median age at diagnosis was 7 weeks (range, 1 week to 7 months). | Cow's milk, soy, corn | 0.6 g protein/kg body weight. 0.15-0.3 g protein/kg body weight for patients with history of severe reactions with small ingestion | Positive challenges elicited symptoms 1 to 4 hours after ingestion of the challenge substance. | 11 (68.7) | IVF = 7 (43.7)Steroid = 3 (18.7)Hypotension = -Admission to ICU = -Severe reactions* = 7 |
| Caubet 2014 (12) | 15 months (median) IQR (9.24) | Cow's milk, soy and solid foods | 0.06-0.6 g of food protein/kg body weight (usually 0.3 g of protein/kg body weight; maximum, 3 g of protein) in 3 equal doses over a 45-minute period and remained under observation for 4 to 8 hours after the ingestion of the challenge food. In the case of grains with low protein content, such as rice and oat, an age-appropriate food portion was served. | From the first-dose: mean 150 min (range 35-370 min) From the last dose: mean 120 min (range: 5-320 min) | 61 (83) | IVF = 70 (96) Hypotension = 14 (19) Admission to ICU = 0Steroids = 69 (94)Ondansetron = -Admission to ED or ICU or hospitalized = 0 Severe reactions* = - |
| Miceli Sopo 2012 (5) | 1 year and 1 month to 5 years and 5 months | Cow's milk and egg well cooked and mixed with wheat | Three different methods: Rome: 50% serving size for age with 2-h observation and then full serving size for age with 4-h observation. Florence: 25%, 50%, and full serving size for age, each followed by 4-h observation Benevento: 0.4 g protein/kg body weight in 3 equal doses over 3 h with 4-h observation, then full serving size followed by 2-h observation | Median time: 2 h (range, 0.5-4 h) (not specified from which dose) | 35 (53) | IVF or steroids = 15 (43) Ondansetron = -Hypotension = -Admission to ICU = -Severe reactions* = - |
| Lee 2017 (53) | Median age 17 months (IQR 10.851.3) | Cow's milk, egg, fish, rice | a single serving size of the food allergen (at least 3 g of food protein, rice at least 1 g), with a 4-hour observation period. | Median time: 2.5 h (2-3h) | 20 (25) | IVF = 6 (20) Steroids = -Ondansetron = 13 (65) Hypotension = 1 (5) Admission to ICU = 0 Severe reactions* = - |
| Fogg 2006 (58) | 15.6 months (range 5-30 months) | Cow's milk, egg, soy, wheat, rice, oat, | 0.05-0.15 g protein/kg body weight of the suspected protein in two increasing doses over a 30-min interval | Mean time: 2.8 ± 0.8 h from the last dose | 15 (80) | IVF = -Steroids = -Ondansetron = -Hypotension = 0 Admission to ICU = 0 Severe reactions* = - |
| Vaquez Ortiz 2017 (75) | 0-18 years | Cow's milk, egg, rice, corn, fish, | an age-appropriate portion (0.3 g/kg and 3 g as maximal dose) divided into 3 equal doses given at 90-minute intervals, except for cow's milk in which 7 consecutive doses were given at 90-minute intervals.) | After the first dose: 0 After the second dose: 12 pts (36.4%) After thethird dose: 17 pts (51%)After the fourth dose: 1 pts (3%) After the fifthdose: 3 pts (9%) | 33 (41) | IVF = -Steroids = -Ondansetron = -Hypotension = 0 Admission to ICU = 0 Severe reactionns* = - |
| Barni 2019 (76) | 12.7 ± 16.4 months (range 1-93 months) | Cow's milk, fish, grain, egg, other | OFC protocol consisted in administering 25% of the full dose, calculated as 0.3 g of food protein/kg body weight, and the remaining dose 4 hours later, followed by another 4 hours of observation. If the patient had a previous history of severe reactions, a lower dose of 0.06 g protein/kg body weight was used. | Mean time latency: 136 min (range 60-230 min; median: 120 min) from the first dose | 19 (35.2) | IVF = 11 (57.9) Steroids = 14 (73.7)Ondansetron = 15 (78.9)Hypotension = 0 Admission to ICU = 0 Severe reactions* = 9 (47) |
| Guenter 2020 (79) | Median age 18.5 months (range 6-118 months, 0.59.8 years). | Uncooked milk, soy, rice, lightly cooked egg, baked egg, cooked, cheese, peanut, and pork | doses ranged from 0.03-0.6g food protein/kg body weight divided in 3 equal doses over 30 minutes | all reactions occurred within 2-3 hours after completion of the initial dose | 10 (11) | IVF = 1 (10)Steroids = 0 Ondansetron = 9 (90) Epinephrine = 1 (10)Hypotension = -Admission to ICU = -Severe reactions* = - |
| Wang 2019 (78) | 2.8 years (average age) | 19 different foods (most frequently milk, soy, wheat, oat, rice, egg, corn, etc.) | Two different protocols: before July 2016 patients received a 2-dose challenge, receiving a cumulative of one-quarter to one-third serving size for age. After July 2016, food challenges were performed by a 1-dose protocol: administration of one-third of serving size for age. After a 4-hour observation period | Symptoms occurred at least 85 minutes after dosing. In the majority (76%) the symptoms started at least 120 minutes after dosing. | 17 (56) | IVF = 14 (82.3) Steroids = -Ondansetron =12 (70.6) Hypotension = 2 (11.7) Admission to Emergency department = 5 (29.4) one of these in ICU = 1 (5.8) Severe reactions* = 5 (29.4) |
| Total | 333 | IVF = 124 /290 (42.7)Hypotension = 20 244 (8.1)Admission in ICU o Emergency Department= 13/238 (5.4) |