1.1 General Population

Prevalences within the author's selected populations are listed. Those that are assigned randomly selected ("unselected") with numbers more than 500 may be regarded as representative of the "general population". Inclusion criteria may involve circumstances not related to atopic predisposition according to current knowledge.
 

Country / Subjects	Sensitivity / Allergy to	References
Australia, Melbourne 620 unselected children (age of <2 years)	cow's milk 2.0%	Hill et al. 1997, 1999
Canada 3000 unselected children (private practice)	cow's milk 0.3% (case history)	Collins-Williams 1956
Canada 787 unselected children (<3 years of age)	cow's milk 7.5% (2 open challenges)	Gerrard et al. 1973
Denmark, Odense a) 1749 unselected newborns b) 52% exclusively brest-fed infants	a) cow's milk 2.2% b) cow's milk 1.0% (elimination/challenge)	Host et al. 1988 Host & Halken 1990
Estonia 251 consecutive born infants	cow's milk 1.2%, 0.8% (SPT) at 6 and 12 months	Julge et al. 1997
Finland unselected children (<6 months of age)	cow's milk 1.3-1.9% (with intestinal form only: 0.06%)	Kuitunen et al. 1985
Finland, Helsinki 866 children from well-baby clinic (1-6 years of age)	cow's milk 2-5% (open challenge)	Kajosaari 1982
Germany 1235 unselected preschool children (5-6 years)	cow's milk 3.9% (SPT)	Schäfer et al. 1999
Iceland, Reykjavik 502 unselected adults	cow's milk 1.2% (RAST)	Gislason et al. 1999
Netherlands, Maastricht 1158 unselected newborns (followed prospectively from birth to 1 year of age)	cow's milk 2.8% (elimination / challenge tests)	Schrander et al. 1993b
Sweden 1397 unselected adults (20-44 years of age)	cow's milk 1.0% (RAST, questionaire)	Björnsson et al. 1996
Sweden, Linköping healthy girls at birth and mean age of 3, 8, 25, and 48 months (n=57-86, all Rh negative)	cow's milk 0%, 4.6%, 9.0%, 0%, 1.2% (RAST)	Hattevig et al. 1984
Sweden, Malmö 1079 unselected children (age at onset 2-44 weeks)	cow's milk in 1.9% (elimination / challenge tests)	Jakobsson & Lindberg 1979
Sweden, Uppsala 414 unselected adults	cow's milk 0.7% (RAST)	Gislason et al. 1999
Turkey, Adana 1348 unselected children (age 15 weeks)	cow's milk in 1.6% (elimination / challenge tests)	Altintas et al. 1995
UK, Isle of Wight 609 unselected newborns	cow's milk 2.5% (case history)	Hide & Guyer 1983
UK, Isle of Wight unselected children (birth cohort of 1456 consecutively born children)	cow's milk in 4.1% (SPT)	Dean 1997
USA appr. 1000 unselected infants (private practice)	cow's milk appr. 7% (case history)	Clein 1951
USA 403 unselected infants (well-baby clinic)	cow's milk 1% (history, skin test)	Bachman & Dees 1957
USA 299 unselected newborns	cow's milk 1% (history, skin test)	Mueller et al. 1963
USA, Denver, CO 480 unselected children (age of 0 to 3 years)	cow's milk 2.2% (challenge tests)	Bock 1987

1.2 Subjects with Atopic or Other Diseases
 

Country / Subjects	Sensitivity / Allergy to	References
Finland, Oulu 57, 43, and 42 children with atopic dermatits	cow's milk 12%, 9.3%, and 7.1% in patients < 1 year, 1-3 years, and 3-15 years of age (SPT)	Hannuksela 1987
Finland, Tampere 113 infants with atopic eczema (age of 2-24 months)	cow's milk 48% (oral challenge)	Kekki et al. 1997
France 81 cases of anaphylactic shock to food (from 1991-1992)	cow's milk 6.5%	Moneret-Vautrin & Kanny 1995
France 80 cases of food- related anaphylaxis (from 1993-97)	cow's milk 6.3% (reported to CICBAA databank)	European Commission 1998
France, Pierre Benite a) 580 patients with adverse reactions to food b) 60 cases of anaphylaxis (study period 1984-92)	a) cow's milk 18% b) cow's milk 3.3%	Andre et al. 1994
France, Nancy and Toulouse 544 food allergic children	cow's milk 8.3%, goat's milk 0.3% (food challenge)	Rance et al. 1999b
France, Toulouse 142 food allergic children	cow's milk 9.2 % (labial food challenge)	Rance & Dutau 1997
France, Toulouse 378 food allergic children	cow's milk 12% (food challenge)	Rance et al. 1999a
Germany,Berlin 107 children with atopic dermatitis (and suspicion of food allergy)	cow's milk 51% (n=92, DBPCFC)	Niggemann et al. 1999b
Germany,Bonn 150  food allergic children (egg white, milk, cod fish, wheat, peanut and/or soybean)	cow's milk 52.0% (RAST)	Liappis & Starke 1999
Italy, Bari 134 patients with atopic dermatitis	cow's milk 13% (case history), 21% (RAST)	Bonifazi et al. 1978
Italy, Florence 54 episodes of food-dependent anaphylaxis in 44 children (age of 1 month to 16 years) (from 1994-1996)	cow's milk 22% goat's milk 4%	Novembre et al. 1998
Italy, Palermo 204 children (median age of 6.3 months) with gastroesophageal reflux	cow's milk 9.3% (history) cow's milk 46% (RAST, SPT, eosinophils) cow's milk 42% (challenge test)	Iacono et al. 1996
Italy, Rome 371 children with food allergy	cow's milk 54% (RAST)	Giampietro et al. 1992
Japan, Tokyo 39 children with positive food challenge	cow's milk 28% (food challenge)	Iwasaki et al. 1994
Netherlands 131 cases of food- induced anaphylaxis (from 1993-1997)	cow's milk 8.4% (survey, reported to the TNO Nutrition and Food Research Institute)	European Commission 1998
Netherlands, Rotterdam 91 patients with atopic dermatitis	cow's milk 47% (SAFT)	Oranje et al. 1992
Poland 163 food allergic infants	cow's milk 64% (RAST)	Hofman 1994
Poland, Warshaw 153 hospitalized infants with respiratory symptoms	cow' milk 21%	Maciejewski et al. 1995
Singapore 124 children with food-induced anaphylaxis	cow's milk and/or egg 11%	Goh et al. 1999
Spain, Madrid 355 food allergic children	cow's milk 25% (SPT, RAST)	Crespo et al. 1995
Spain, Pamplona 74 patients with atopic dermatitis	cow's milk 37% (SPT, RAST, Histamine Release)	Resano et al. 1998
Sweden a) 61 cases and b) 55 cases of food- induced anaphylaxis (from 1994-1996)	a) cow's milk 20% (reported to the National Food Administration) b) cow's milk 5.5% (Hospital Reports)	European Commission 1998
Switzerland, Zurich 402 food allergic adults	cow's milk 16% (cheese only 6.2%, milk only 3.5%)	Wüthrich 1993
Switzerland, Zurich 383 food allergic patients (study period 1990-94)	cow's milk 11% cheese 5.7%	Etesamifar & Wüthrich 1998
Thailand 100 asthmatic children	milk 2% (SPT)	Kongpanichkul et al. 1997
UK, London 100 patients with food intolerance	cow's milk 46%, cheese only 5% (repeated challenge)	Lessof et al. 1980
UK, Manchester 172 patients expierenced anaphylactic reactions to foods (from 1994-1996)	cow's milk 1.7% (suspected cause of patients' worst reaction)	Pumphrey & Stanworth 1996
USA, Baltimore, MD 196 food-allergic patients with atopic dermatitis	cow's milk 50% (n=109, DBPCFC)	Sampson & Ho 1997
USA, Baltimore, MD 11 beef-allergic patients (DBPCFC)	cow's milk 73% (DBPCFC)	Werfel et al. 1997a
USA, Denver, CO 180 food allergic children	cow's milk 23% (DBPCFC)	Bock & Atkins 1990
USA, Little Rock, AR 165 patients with atopic dermatitis	cow's milk 19% (SPT) from which 50% were DBPCFC-positive	Burks et al. 1998
USA, New Haven, CT 98 infants and children with multiple gastrointestinal allergies	soy and milk 62% milk and gluten 3%	Gryboski & Kocoshis 1980
USA, New Haven, CT 38 children with ulcerative colitis (age of <10 years)	cow's milk 13% (history)	Gryboski 1993
USA, OH 148 respiratory-allergic children with reproduced symptoms after food challenge	cow's milk 29%	Ogle et al. 1980

1.3 Prevalence of Associated Allergies
 

Country / Subjects	Sensitivity / Allergy to	References
Australia, Parkville 42 children with CMA (followed for 2 years)	egg 67%, peanut 55% (challenge test)	Hill et al. 1994
Finland, Helsinki 19 children with CMA	soybean 32%	Paganus et al. 1992
Sweden, Malmö 20 infants with CMA (age of <12 months)	soybean in 35%	Jakobsson & Lindberg 1979
Thailand, Bangkok cow's milk-sensitive children	soybean 17%	Harikul et al. 1995
USA, New Haven, CT 98 infants and children with multiple gastrointestinal allergies	soy and milk 62% milk and gluten 3%	Gryboski & Kocoshis 1980
USA, San Diego, CA cow's milk-sensitive infants	soybean 25%	Wilson & Hamburger 1988
USA, San Diego, CA 93 children with CMA (<3.5 years)	soybean 14 % (DBPCFC, open challenge, or convincing history of an anaphylactic reaction)	Zeiger et al. 1999

2 Outgrowing of Cow's Milk Allergy
 

Country / Subjects	Sensitivity	References
Australia, Victoria 47 with CMA (age of  3-66 months) with onset of symptoms a) <1 hour (n=15), b) 1 to 20 hours (n=24) or, c) >20 hours (n=8)	Oral tolerance acquired at follow-up of 16 months in: a) 40%, b) 42%, c) 25% of patients	Hill et al. 1989
Australia, Victoria 97 children with CMA	Tolerance in 28% by 2 years, in 56% by 4 years, and 78% by 6 years of age (DBPCFC)	Bishop et al. 1990
Canada 150 children with CMA	Tolerance in 6% by 1 year, 20% by 2 years, in 30% by 3 years, and 53% by 12 years of age	Gerrard et al. 1967
Denmark, Odense 39 children with CMA	Total recovery in 56% by 1 year, 77% by 2 years, and 87% by 3 years of age; cow's milk allergy persisted in 24% of patients with early IgE sensitization to cow's milk	Host & Halken 1990
Finland, Tampere 37 patients with a history of CMA (mean age of 28 months)	Oral tolerance acquired at follow-up of 13 months in 65% of patients	Isolauri et al. 1992
France, Nancy and Toulouse 68 children with CMA	Sensitivity to cow's milk according to age groups: 0-1 year in 22% 1-3 years in 56% 3-6 years in 19% 6-15 years in 2.9% (SPT and/or RAST, food challenge)	Rance et al. 1999b
Italy, Rome 37 children with CMA	Tolerance acquired in 68% at age of 2 years; 33% did not tolerate cow's milk at age of 6 years	Businco et al. 1985
Japan, Gifu 22 children with CMA and atopic dermatitis	41% Improvement rate in children aged from <1 year to >6 years	Iida et al. 1995
Netherlands, Groningen 23 children with CMA	Oral tolerance acquired in 13%, 48%, 74% and 78% of children at the age of 1, 2, 3 and 4 years, respectively	Olsder et al. 1995
Netherlands, Maastricht 37 children with CMA	Oral tolerance acquired in 15%, 22%, 51% and 67% of the children at the age of 1, 2, 3 and 4 years, respectively; 90% with initial IgE levels <10 kU/L and 47% with initial IgE >/= 10 kU/L became tolerant	Schrander et al. 1992
Switzerland, Zurich 34 adults with CMA	Oral tolerance acquired in 28% after 4 years of disease	Stoger & Wüthrich 1993
Turkey, Adana 21 children with CMA (age 15 weeks)	29% recovered within 2 years	Altintas et al. 1995
USA Food allergic patients	soy, egg, milk, wheat, and peanut: 26% loss (after 1 year of onset, DBPCFC)	Sampson & Scanlon 1989
USA, Baltimore, MD 29 children with CMA	Tolerance acquired in 38% at median age of 3 years (DBPCFC)	James & Sampson 1992

3 Symptoms of Cow's Milk Allergy
 

Symptoms & Case Reports

systemic reactions anaphylaxis (20, 21, 24, 36, 40, 46, 44, 53, 54, 55, 62, 68, 69, 73, 74), excercise induced anaphylaxis (54, 60, 72), fatal reactions (47a, **48) cutaneous symptoms angioedema (8, 18, 17, 44, 54, 74), atopic dermatitis (22, 23, 24, 27, 35, 74), contact urticaria (19), dermatitis (66), eczema (3, 6, 8, 9, 17, 25, 29, 30, 50, 67), erythema (29, 54), exanthema (6), lips edema (10), pruritus (2), redness (54), swelling of eyelids (54), urticaria (2, 6, 8, 10, 17, 18, 22, 23, 26, 30, 39, 44, 50, 54, 67, 74), chronic urticaria (61) gastrointestinal symptoms abdominal cramps (2), abdominal distention (42), abdominal pain (44), colic (3, 50, 66), infantil colic syndrome (1, 5, 6), colitis (56, 63), constipation (3, 66), chronic constipation (48, 51), diarrhea (2, 3, 6, 10, 11, 15, 17, 25, 29, 39, 42, 44, 50, 66, 67), chronic diarrhea (12), food protein-induced enterocolitis syndrome (absence of specific IgE) (69), eosinophilic colitis (31), eosinophilic gastroenteritis (28), gastroenteritis (11), gastro- oesophageal reflux (13, 57, 58, 65), morphologic lesion (15), nausea (44), proctitis (32), progressive small bowel mucosal damage (26), occult intestinal bleeding (4), oropharyngeal itching / swelling (39, 44), oropharyngeal pruritus (71), edema of tongue (10), acute pancreatitis (33), loose stools (67), vomiting (2, 3, 6, 11, 17, 22, 25, 66, 67), in general (30, 74) respiratory symptoms allergic alveolitis (7, 16), asthma (3, 10, 11, 18, 22, 39, 44, 45, 47, 49, 54, 68, 73), bronchospasm (29), bronchitis (6, 17), conjunctivitis (73), coughing (25, 50), dyspnea (50, 54, 71), nasal blockade (71), allergic rhinitis (22), rhinitis (29, 44, 54), rhinoconjunctivitis (44, 45, 54), serous rhinorrea (71), sneezing (71), wheeze (25, 50, 66) other symptoms association with cytomegalovirus colitis* (64), infantile autism* (52), anal fistula and fissures (48), growth retardation / failure to thrive (3, 6),  insomnia (14), iron deficiency anemia in 20-70% (11), lactic acidosis (75), Melkersson-Rosenthal syndrome* (59), migraine* (38), necrotizing enterocolitis (43), steroid- resistant nephrotic syndrome (41), pallor (17), psychological disturbance (3), pulmonary hemosiderosis (34), tension-fatigue syndrome (37), lethargy (69) * controversial / hypothetical, ** possibly due to partially hydrolyzed whey formula

(1) Harris et al. 1977 (2) Bonifazi et al. 1978 (3) Buisseret 1978 (4) Ivady et al. 1978 (5) Jakobsson & Lindberg 1978 (6) Jakobsson & Lindberg 1979 (7) Chetty 1982 (8) Firer et al. 1982 (9) Taylor et al. 1982 (10) Businco et al. 1983a (11) Podleski et al. 1984 (12) Businco et al. 1985 (13) Forget & Arends 1985 (14) Kahn et al. 1985, 1987 (15) Kuitunen et al. 1985 (16) Vergesslich et al. 1985 (17) Hill et al. 1986 (18) Koers 1986 (19) Salo et al. 1986 (20) Wüthrich & Hofer 1986 (21) Jarmoc & Primack 1987 (22) Host & Samuelsson 1988 (23) Prahl et al. 1988 (24) Businco et al. 1989 (25) Hill et al. 1989 (26) Iyngkaran et al. 1989 (27) Cantani et al. 1990 (28) Hill & Milla 1990 (29) Husby et al. 1990 (30) Isolauri et al. 1990 (31) Wilson et al. 1990 (32) Lake 1991 (33) de Diego et al. 1992 (34) Fossati et al. 1992 (35) James & Sampson 1992 (36) Jones et al. 1992 (37) Kondo et al. 1992 (38) Mylek 1992 (39) Norgaard & Bindslev-Jensen 1992 (40) Sampson et al. 1992 (41) Sieniawska et al. 1992 (42) Hayashi et al. 1993 (43) Michaud et al. 1993 (44) Stoger & Wüthrich 1993 (45) Bernaola et al. 1994 (46) Businco et al. 1994 (47a) Malmheden Yman et al. 1994 (47) Rossi et al. 1994 (48) Tarim et al. 1994 (49) Vargiu et al. 1994 (50) Altintas et al. 1995 (51) Iacono et al. 1995a (52) Lucarelli et al. 1995 (53) Moneret-Vautrin & Kanny 1995 (54) Wüthrich & Johansson 1995 (55) Wüthrich et al. 1995 (56) Armisen Pedrejon et al. 1996 (57) Cavataio et al. 1996 (58) Iacono et al. 1996 (59) Levy et al. 1996a (60) Levy et al. 1996b (61) Paranos & Nikolic 1996 (62) Tabar et al. 1996 (63) Weisselberg et al. 1996 (64) Jonkhoff-Slok et al. 1997 (65) Iacono et al. 1998a, 1998b (66) Iacono et al. 1998c (67) Jarvinen et al. 1998 (68) Kanny et al. 1998 (69) Laoprasert et al. 1998 (70) Sicherer et al. 1998 (71) Vila Sexto et al. 1998 (72) Fiocchi et al. 1999 (73) Goh et al. 1999 (74) Rance et al. 1999b (75) Rizk et al. 1999

Percentage of Reactions	References
Symptoms / Ref. (1)  (2)  (3) (4)  (5) (6)  (7) (8)  (9) (10) (11) Anaphylaxis 5% 100%     5%       2%   7.8% Cutaneous       64%   31% 79% 93%    58%   + Gastrointestinal                   19%   + Respiratory                   13%   All 3 organ systems                   4%   Atopic dermatitis 41%   21%         100%   100% 50% Conjunctivitis                     3.1% Urticaria / Angio-oedema                     28% Angio-oedema   66%     65%       13%     Urticaria 10%     100%             Generalized urticaria   69%     45%       10%     Contact urticaria   59%     80%             Eczema         33%       13%     Circumoral lesions                 26%     Gastrointestinal       59%   50% 42% 65%    4% 7.8% Vomiting 34%       13%       41%     Diarrhoea 47%       3%       48%     Colic                 14%     Colitis                 4%     Abdominal pain 41%                     Respiratory       33%   19% 91% 48%    2%   Allergic rhinitis 43%   43%   28%       21%     Asthma 37% 55% 40%                 Cough / Wheeze   48%     65%       29%     Other 6%                     Failure to thrive                 22%     Gastro-oesophageal reflux                 6%     Convulsion         2%       2%     No. of patients 45 29 97 39 75 26 34 54 100 47 68	(1) Goldman et al. 1963a (2) Schwartz et al. 1987 (3) Bishop et al. 1990 (4) Host & Halken 1990 (5) Schwartz 1991 (6) Schrander et al. 1993b (7) Stoger & Wüthrich 1993 (8) Sampson & Ho 1997 (9) Hill et al. 1999 (10) Niggemann et al. 1999b (11) Rance et al. 1999b Children with CMA diagnosed by (1) clinical history, oral challenge (2) clinical history of anaphylactic reactions, RAST (3) parents reported (4, 6) elimination/challenge (5) clinical history, SPT (8, 10) DBPCFC (11) labial food challenge Adults with CMA diagnosed by (7) clinical history, RAST
Onset of Symptoms Type of Reactions (1) (2) (3) (4) immediate 53%   46% 64% delayed reactions 47%   54% 28% both       8% < 6 hours   51%     within 6-12 hours   13%     within 12-24 hours   10%     > 24 hours   26%     No. of patients 47 125 50 47	(1) Björkstén et al. 1983 (2) Ventura & Greco 1988 (3) Sutas et al. 1997 (4) Niggemann et al. 1999b Children with CMA diagnosed by (1) clinical history (2) elimination / challenge (3, 4) DBPCFC
Age at Onset of CMA Onset in 30% of children with CMA in the first month of life (1) and in 96% at <1 year of age (2)	(1) Savilahti 1981 (2) Bock 1987
Cluster Groups 3 clusters of patients with CMA using a K-means algorithm (data of case history and effects of a standardized milk challenge): Percentage of patients Onset of Symptoms Symptoms Diagnostics a) 27-32% after <45 min predominantly urticarial and angioedematous eruptions positive skin tests, elevated total and milk specific serum IgE b) 51-53% 45 min to 20 hours pallor, vomiting, or diarrhea relatively IgA deficient* (1) c) 17-20% after >20 hours eczematous or bronchitic or diarrheal symptoms positive skin tests and elevated specific IgE only in patients with eczema *milk- specific IgA, IgG and IgM levels similar in all groups and controls (2) (1) 100 cow's milk allergic children (mean age of 6 month) (2, 3) 47 cow's milk allergic children (age 4-66 months)	(1) Hill et al. 1986 (2) Firer et al. 1987 (3) Hill et al. 1989
Threshold of Ingestion Amounts of cow's milk inducing symptoms ranged from 5 g to 250 g  (DBPCFC) (1) Fatal anaphylaxis after ingestion of 100g of a sausage containing 60 mg CAS (2) The quantity of ingested whey proteins elicited anaphylactic reactions in a 3-year-old boy was estimated to be 120-180 µg (equivalent to 23 to 24 µL of milk) (3)	(1) Norgaard & Bindslev-Jensen 1992 (2) Malmheden Yman et al. 1994 (3) Laoprasert et al. 1998

4 Diagnostic Features of Cow's Milk Allergy

[Family History / Maternal Factors] [Humoral Parameters] [Cellular Parameters]
[Gastrointestinal Parameters] [Test Significance] [Other Features]
 

Family History / Maternal Factors	References
Family History Subjects / Follow-up Manifestation of CMA Family History  of Atopic Disease Ref. children (siblings with CMA) in 33% positive (1) formula fed infants (5th day to 3 months) in 40%* positive (2) formula fed infants (5th day to 3 months) in 13%* negative (2) 29 children with severe CMA (1 to 10 months)   in 89% (1 parent) in 50% (both parents) (3) 91 children (8 months) with gastrointestinal symptoms in 34% (14%) (4) 57 children (8 months) with extraintestinal symptoms in 53% (5%) (4) 12 infants (birth to 5 years) persistent** (a) in 83% (5) 26 infants (birth to 5 years) resolved within 1-2 years (b) in 38% (5) *significance P <0.001                       **symptoms at onset predominantly gastrointestinal, at the end of the study increased frequency of wheezing, constipation, and delayed reactions (a, b) multiple food intolerance in a) 92%, and b) 12%, respectively (3) occurence of severe CMA in a pair of identical twins and HLA-identical siblings (4) family history of CMA in paranthesis	(1) Gerrard et al. 1973 (2) Vandenplas & Sacre 1986 (3) Schwartz et al. 1987 (4) Ventura & Greco 1988 (5) Iacono et al. 1998c
Maternal Parameters in Breast Milk Mothers from IgG IgA TGF-beta-1 HLA-DR # Total No. of Leukocytes Ref. 6 infants with CMA   (-)*       (1) 65 infants with IgE-mediated CMA     (-)*     (3) 37 with non-IgE mediated CMA     (+)*     (3) 36 infants with CMA       (-)** (+) (2) 24 healthy infants       (+)** (-) (2) *in colostral breast milk samples, **significance p=0.012 (-) lower, (+) higher values # expression on breast milk macrophages (2) asymptomatic mothers (3) TGF-beta-1 positive correlation to beta-LG spec. IgA and CAS spec. IgG, negative correlation to SPT and lymphocyte stimulation with beta-LG or CAS	(1) Savilahti et al. 1991 (2) Jarvinen et al. 1999a (3) Saarinen et al. 1999b
Maternal Serum IgG (1) Mothers of infants who a) developed allergy or b) presented no symptoms: Statistically lower serum IgG anti- beta-LG levels in a) than in b) (P <0.001)	(1) Casimir et al.1989

 

Humoral Parameters	References
Specifc Serum IgE Positivity and mean values of cow's milk specific serum IgE: Patients / Reference (1) (2) (3) with history of CMA (+) in 71%     cow's milk tolerant children (+) in 27%     cow's milk DBPCFC positive   34 kU/L* 3.9 kU/L** cow's milk DBPCFC negative   1.7 kU/L* 0.6 kU/L** (+) increased IgE levels, *significance P<0.0001, **significance P<0.001 (1) 69 children with food intolerance, IgG levels seemed to parallel IgE levels, no differences in IgA levels in allergic and control subjects (2) 196 children and adolescents with atopic dermatitis (90% family history of atopic diseases) (3) 107 children with atopic dermatitis	(1) Dannaeus et al. 1977 (2) Sampson & Ho 1997 (3) Niggemann et al. 1999b
Specific IgE, Persistent Allergy Significantly elevated levels of milk- and CAS- specific IgE in children with persitent cow's milk allergy (age of >9 years) as compared to children with CMA at the age of <3 years (RAST) (1)	(1) Sicherer & Sampson 1999
Specific IgE, Immediate Reactors, Tolerance 69 IgE- sensitized immediate reacting children with CMA (median age of 24 months) median study period of 2 years: 22% developed clinical tolerance, had lower specific IgE levels at the beginning and the end of study period, and significant fall in SPT reactivity (1)	(1) Hill et al. 1993b
beta-LG Specific B Cell Epitopes, Immediate and Delayed Type CMA 8 immediate type patients with CMA (systemic reactions) and 6 delayed type patients with CMA (skin reactions) recognized same B cell epitope (beta-LG aa 95-113), no difference in IgE- binding peptide pattern (RAST inhibition, Pin-ELISA) (1)	(1) Heinzmann et al. 1999
Specific Serum IgG and IgA Percentage of positivity of specific serum IgA and IgG antibodies: Specificity IgA IgG Ref. alpha-LA a) 43% b) 44% a) 57% b) 69% (1) beta-LG a) 71% b) 50% a) 43% b) 75% (1) beta-LG   a > b (2) beta-LG   a, c > b (3) BSA   a > b (2) BSA   a, c > b (3) CAS a) 86% b) 44% a) 86% b) 69% (1) CAS   a > b '' (3) pooled alpha-LA, beta-LG, CAS a) 71% b) 38% a) 57% b) 63% (1) NS = no significant differences (1) children (age of 3 months to 6 years): a) 7 with CMA (cutaneous symptoms), b) 16 with CMA (gastrointestinal symptoms) (2) a) 10 infants fed cow's milk- based formula, b) 10 infants fed a CAS hydrolysate formula until the age of 9 months (3) 129 children a) cow's milk formula fed, b) CAS hydrolysate formula fed, c) breast fed during the first 3 days of life, otherwise exclusively breast fed, follow-up for 2 years ('' at 8 and 12 months)	(1) Bottaro et al. 1992 (2) Vaarala et al. 1995 (3) Juvonen et al. 1999
Specific IgE and IgG Subclass, IgA, Ratios spec. Ig Cow's Milk CAS beta-LG IgE   a > b (4); + (8) a > b (4) IgE/IgG   a > b (4) a > b (4) IgG1   a > b (4); + (8) c > d, e, f** (6); + (8) IgG4 NS (1) a > b > c (2) a > b > c (2) a > b (4) a > c; b > c (2) + (8) IgE/IgG1   a > b (4) a > b (4) IgE/IgG4   a > b (4) a > b (4) IgG (+) (3) (-) NS (5) NS (4) NS (4), NS (7) IgA (-) (3)     (+) increase, (-) decrease, (NS) no significant differences **ratios of IgG1/IgG, IgG1/IgG3 and IgG1/IgG4 same tendency (1) no relation to provocation test in 14 children with immediate reactions to cow's milk, 15 cow's milk tolerant children (2) children with immediate type CMA, SPT positive to a) cow's milk (n=20), b) cow's milk and whey hydrolyzed formula (n=17), c) cow's milk, whey and CAS hydrolyzed formulas (n=13) (3) 21children with challenge proven CMA (4) a) 18 children with CMA, b) 11 children acquired tolerance (5) 28 adults with CMA (aged from 16 to 58 years) (6) c) children with CMA predominantly gastrointestinal , or d) skin symptoms of immediate-onset, e) children with untreated coeliac disease and f) healthy children (7) a) 12 children with persistent CMA up to age of 5 years, b) 26 controls (8) 15 adults with CMA (average age of 39.5 years)	(1) Björkstén et al. 1983 (2) Schwartz 1991 (3) Tainio & Savilahti 1990 (4) James & Sampson 1992 (5) Stoger & Wüthrich 1993 (6) Saalman et al. 1995 (7) Iacono et al. 1998c (8) Little et al. 1998
Symptoms and Prevalence of Specific IgE Positivity of cow's milk specific serum IgE in 148 children with CMA according to symptoms: Symptoms IgE Symptoms IgE Respiratory 100% Persisting diarrhea 33% Eczema 71% Severe colics 27% Urticaria / Anaphylaxis 56% Total 48% Vomiting 47% Gastrointestianl 33% Failure to thrive 33% Extraintestinal 72%	Ventura & Greco 1988
Serum Eosinophilic Cationic Protein (ECP) After 4 weeks of elimination diet; measurement of ECP before oral cow's milk challenge, 27 hours and 1 week after in 28 cow's milk allergic children (age of 5.8 to 43 months): Increased, transient ECP serum levels during challenge in patients with skin manifestations but not in patients with gastrointestinal symptoms (1)	(1) Suomalainen et al. 1994b
Soluble IL-2 Receptor Elevated serum levels of soluble IL-2 receptor in 16 children with non- IgE mediated CMA and in 8 children with IgE mediated CMA as compared to 19 children with other IgE-mediated food intolerance (1)	(1) Blanco Quiros et al. 1993
Specific TABM Elevated serum levels of T-cell derived antigen- binding molecules (TABM) specific for alpha-LA, beta-LG, and CAS in 6 to 7 of 15 adults with CMA (1)	(1) Little et al. 1998

 

Cellular Parameters	References
Lymphocyte Subclasses, Antigen Expression Patients T-Cells B-Cells PBMC Ref. 29 children with severe CMA     (NS) HLA-A, -B, -DR (1) 7 children with CMA and atopic dermatitis (+)*  CLA+     (2) children with CMA (+) CD8+     (3) 37 children with CMA (+)*  HLA-DQ7     (4) 24 children with CMA (0.4-10 months) (-)* CD8+ (+)* total No. (+)* CD19+   (5) 9 children with IgE-CMA  (+)* alpha4beta7 integrin   (NS) CD3+CD4+ (-)* CD3+CD8+ (6) 15 fed with cow's milk formula     (+)* PCNA (7) 7 breast fed children     (+)* CD23+ (7) (+) increase, (-) decrease, * significant, (NS) no significant difference (1) preparations from unstimulated PBMC (2) in vitro stimulation with CAS (3) stimulation with alpha s1-CAS (4) majority of HLA-DQ7 positive patients presented a high humoral response rather than cellular response (stimulation with beta-LG) (5) challenge proven patients, compared to healthy controls (no stimulation) (6) mean age of 28 months (7 months to 9.3 years), beta-LG stimulated PBMC (7) children with IgE- mediated CMA (3-11 months of age), PCNA expression >/=10% as specific and sensitive marker of CMA in cow's milk fed infants, low cow's milk antigen diets are related with reduced lymphocyte reactivity in whey hydrolyzed fed and breast fed infants (stimulation with beta-LG) CLA - cutaneous lymphocyte antigen (responsible for skin homing) PCNA - proliferating cell nuclear antigen	(1) Schwartz et al. 1987 (2) Abernathy-Carver et al. 1995 (3) Nakajima et al. 1996 (4) Camponeschi et al. 1997 (5) Jarvinen et al. 1998 (6) Eigenmann et al. 1999 (7) Papadopoulos et al. 1999
Lymphocyte* / PBMC** Proliferation Patients / Stimulation with Cow's Milk Proteins beta-LG BSA CAS Ref. 17 children with CMA   (+) (+)   (1)* children with CMA (challenge proven)   (+)     (2)* a) children with CMA b) children with CMA (immediate type, RAST positive)   a) (+) b) (-) a) (+) b) (-)   (3)** children with CMA and atopic dermatitis     (+)   (4)** a) children with CMA (gastrointestinal symptoms) b) children with CMA (skin or no symptoms) a > b       (5)* 10 children with CMA NS''     NS (6)** a) <5 years, b) >6 years of age     a > b   (7)** a) 10 infants fed cow's milk- based formula b) 10 infants fed a CAS hydrolysate formula   a > b a > b a > b'' (8)** a) 27 children with IgE mediated CMA b) 9 children with milk induced enterocolitis syndrome a) (+) a vs b: NS       (9)* a) 22 patients with cow's milk responsive atopic eczema b) 66 patients with atopic eczema (non-responsive)       a > b (10)** (+) higher stimulation index or proliferation, (NS) no significant differences ------------------- (1) significant proliferation with at least one milk antigen in 15 patients (2) in children without specific IgE (3) 3 children with CMA and  tension- fatigue sydrome (cow's milk RAST scores in a) negative or slightly positive) (4) as compared to children with immediate allergic symptoms and controls  (5) 44 children with CMA (mean age of 16 months) after 2-4 weeks of elimination diet, proliferation response abrogated after clinical challenge (6) as compared to control group ('' stimulation with whey hydrolyzed formula and proteins), lower stimulation with hydrolyzed formula (7) 22 children with CMA and atopic dermatitis, proliferative response decreased rapidly after elimination diet (8) fed until the age of 9 months ('' stimulation with alpha-CAS) (9) a) as compared to control group (significant, but extensive overlapp), group a) also responded to soybean antigen (10) age of 16-67 years (median 28 years)	(1) Endre & Osvath 1975 (2) Tainio & Savilahti 1990 (3) Kondo et al. 1992 (4) Kondo et al. 1993 (5) Suomalainen et al. 1994a (6) Eigenmann et al. 1995 (7) Iida et al. 1995 (8) Vaarala et al. 1995 (9) Hoffman et al. 1997 (10) Werfel et al. 1997b
Lymphocyte Transformation Lymphocyte transformation test a) before and b) 30 days after elimination of cow's milk from the diet: a) significantly increased lymphoblastogenesis (P <0.01), b) no differences in 19 children with CMA (1)	(1) Brarda et al. 1989
CBMC Proliferation, IFN-gamma Stimulation of cord blood mononuclear cells (CBMC) with cow's milk proteins: pronounced proliferation of cells stimulated with alpha-LA, beta-LG, and alpha-CAS; preferentially reduced IFN-gamma levels in individuals with positive parental allergic history (39 randomly selected newborns)  (1)	(1) Szepfalusi et al. 1997
Cytokine Production by Lymphocytes Patients / Cytokines IFN-gamma TNF-alpha IL-4 Ref. a) immediate- reacting  b) late- reacting c) milk tolerant a < c, b*     (1) a) children with CMA b) children who acquiered tolerance a < b < c     (2) children with CMA   (+)   (3, 4) a) children with CMA b) children who acquiered tolerance   a > b   (4) a) immediate- reacting  b) late- reacting a) (+) b) (-)     (5) children with atopic dermatitis (milk responsive)     (-) (6) a) children with CMA (cutaneous symptoms) b) children with CMA (predominantly digestive symptoms) d) children who acquiered tolerance   a > b > c, d ('')   (7) 31 children with CMA (-)* (-)*   (8) * significant, c) healthy control group, (+) positive response (1) 75 (a) and 17 (b) children with CMA and 59 (c) tolerant children (age of 1 to 9 years) (stimulation with beta-LG) (2) 22 children (3, 4) stimulation of PBMC with cow's milk proteins (5) lower thresholds of stimulation in a) as compared to b) (5) 50 cow's milk allergic children (age of 2 to 60 months) (DBPCFC positive) with atopic dermatitis, after DBPCFC difference in IFN-gamma generation abolished  (6) IL-4 production of CD4+  CAS specific T-cell clones (compared to house dust mite sensitive patients) (7) 83 children, measured in whole blood cultured with cow's milk proteins, day 1 ('') followed by TNF-alpha degradation, day 5: secretion peak in group b) (8) challenge proven children with either skin or gastrointestinal symptoms or both compared to healthy controls (age of 0.12-11.2 months), unstimulated PBMC and mitogen- induced production	(1) Hill et al. 1993a (2) Suomalainen et al. 1993a (3) Heyman et al. 1994 (4) Benlounes et al. 1996 (5) Sutas et al. 1997 (6) Werfel et al. 1997b (7) Benlounes et al. 1999 (8) Österlund et al. 1999
Cytokine Secreting Cells in Blood and Duodenal Mucosa Frequency of spontaneously cytokine secreting mononuclear cells  in the   blood duodenal mucosa INF-gamma a, b > c a > c IL-4 b > a > c a > c IL-5 a, b > c a = c IL-10 a, b > c a < c children with a) CMSE, b) CMA, and c) age matched controls Cytokine secreting cells more frequently in duodenal mucosa than in the blood	(1) Hauer et al. 1997
PBMC, Migration Inhibition Factor In vitro assay of lymphocyte migration inhibition factor (MIF), stimulation of peripheral blood lymphocytes with beta-LG: significant higher MIF production in 24 children with CMA than in control subjects; most of 18 children recovered from CMA had negativ assay (1)	(1) Ashkenazi et al. 1980
Lymphocytes, Suppressor Activity Decreased suppressor activity of isolated lymphocytes induced by either Concanavalin A or cow's milk in 10 children with CMA as compared to controls and patients who acquired cow's milk tolerance (1)	(1) Suomalainen et al. 1993b
Cell Mediated Cytotoxicity Antibody- dependent cell- mediated cytotoxicity (ADCC) to beta-LG- coated cells rather induced in most sera of children with CMA and predominantly gastrointestinal symptoms than in sera of children with skin reactions (immediate- type), children with untreated coeliac disease, or healthy children; ADCC reactivity of individual sera correlated with their IgG1 antibody levels (1)	(1) Saalman et al. 1995

 

Gastrointestinal Parameters	References
Salivary IgA 158 healthy mature infants at birth: Salviary anti-CAS IgA  was significantly higher (P <0.05) in high risk infants than in no risk or low risk infants; salviary anti-CAS IgA  values correlated with maternal allergy, but not with paternal allergy (1)	(1) Renz et al. 1990
Pancreatic Enzymes children with CMA (median age 3 months) fed with a) a hydrolyzed CAS- based formula or b) a soy- protein based formula: No significant difference in pancreatic secretion between both groups for any of the enzymes studied (trypsin, chymotrypsin, lipase, and phospholipase) during diet of  6 weeks (1)	(1) Carroccio et al. 1997
Duodenal Fluid, Specific IgE and IgD increased levels of cow's milk protein (and soybean agglutinin) specific IgE and IgD in basal and pancreozymin- stimulated duodenal fluid in 13 children with various intestinal diseases (1)	(1) Freier et al. 1983
Jejunal Fluid, Hyaluronic acid, Albumin Jejunal fluid levels of hyaluronan (hyaluronic acid) and albumin increased after milk perfusion challenges in 5 adults with CMA (DBPCFC positive, SPT and RAST negative, lactose tolerant) as compared with control group (1)	(1) Bengtsson et al. 1996
Small Intestine Mucosa, IgE and IgM Plasma Cells local reaginic reaction after ingesting cow's milk: increased mucosal IgE and IgM plasma- cells, increased degranulation of mast cells, staining of connective tissue and basement membranes with antisera to IgG and C3 complement in 2 cow's milk sensitive infants (1)	(1) Shiner et al. 1975
Small Intestine Mucosa and Serum, Alkaline Phosphatase Levels of alkaline phosphatase (ALP) after cow's milk protein challenge: Significant depletion in upper jejunal mucosa tissue and serum in infants with clinical and histological reactions (n=10); tissue ALP depressed in 3/5 patients with histological but no clinical reactions to cow's milk (1)	(1) Iyngkaran et al. 1995
Small Intestinal IgE Plasma Cells, Specific Serum IgE Patients / Cow's Milk Specific IgE Plasma Cells Serum IgE Ref. 16 children  with CMA (+) in 56% (+) in 38% (1) 15 without CMA (+) in 6.7% (+) in 13% (1) (1) elimination / challenge proven CMA	(1) Schrander et al. 1993a
Intestinal Total Immunoglobuline Secreting Cells Intestinal immune responses after diagnostic milk provocation: Patients / No. of Secreting Cells IgM IgA IgG Ref. a) with CMA (acute urticaria) (+) (-) (-) (1) b) with CMA (gastrointestinal symptoms) (+) (+) (-) (1) c) with CMA (skin and gastrointestinal symptoms) (+) (+) (+) (1) d) 13 with persistent CMA (+) (+) (+) (2) e) 24 acquired tolerance (-) (-) (-) (2) d) 27 with CMA (age of 9-69 months) (+) (+) (+) (3) (+) significant increase during challenge, (-) no increase (1) IgM and IgA responses: in group b) > a) (3) increase in all isotypes associated with clinically positive cow's milk challenge; specific antibody secreting cells against beta-LG and CAS (and gliadin) increased in IgM class only	(1) Isolauri et al. 1990 (2) Isolauri et al. 1992 (3) Suomalainen et al. 1992
Intestinal Eosinophils, Lymphocytes, Mast Cells Patients Eosinophils Lymphocytes TIA-1** Mast Cells Ref. 12 children with CMA (+) in 58%     (-) (1) 47 children with coeliac disease (+) in 60%     (-) (1) children with CMA and chronic diarrhea (+)*       (2) 21 children with CMA/CMI (+) in 38% (+)*     (3) 35 children with gluten intolerance (+) in 27% (+)*     (3) 10 children with CMA/CMI   (+)* (+)*   (4) * significant, (+) increase, (-) decrease **TIA-1 (= cytotoxic granule-associated protein) expressing lymphocytes (1) in lamina propria of jejunum (2) in lamina propria of duodenal mucosa  (3) cellular infiltration of small intestinal mucosa (4) number of TIA1- expressing intraepithelial lymphocytes (IEL) and the TIA1/IEL ratio in patients on cow's milk-free diet of various duration, negative correlation between the TIA1/IEL ratio and the duration of the diet (duodenal biopsies)	(1) Kosnai et al. 1984 (2) Challacombe et al. 1986 (3) Kaczmarski et al. 1989 (4) Hankard et al. 1997
Intestinal ECP, MBP, Histamine, VCAM-1 Patients ECP* MBP* Histamine* VCAM-1** Ref. 5 adults with CMA (+)   (+)   (1) 14 patients with cow's milk-sensitive enteropathy   (+)   (+) (2) (+) increased, (-) decreased, *intestinal secretion, **expression on mononuclear cells (1) DBPCFC positive, SPT and RAST negative, lactose tolerant patients (perfusion challenges with milk, CAS, and whey) (2) Challenge positive, SPT and RAST negative patients, endoscopic duodenal biopsy ECP = eosinophil cationic protein MBP = eosinophil major basic protein VCAM-1 = vascular cell adhesion molecule-1	(1) Bengtsson et al. 1997 (2) Chung et al. 1999
Intestinal Epithelial Cells, CD23 Expression CD23 expression on intestinal epithelial cells increased in 3 children with CMPI (age < 1 year) associated by high levels of specific IgE	Kaiserlian et al. 1995
Fecal alpha-1 Antitrypsin, TNF-alpha, ECP, IgE Indicators of intestinal inflammation in jejunal fluid after cow's milk challenge: Patients alpha-1 Antitrypsin TNF-alpha ECP IgE  Ref. a) 13 children with CMA (gastrointestinal symptoms)   (+)* (-) (-) (1) b) positive DBPCFC with cow's milk (+) in 43% (+)** (+)***   (2) c) negative DBPCFC with cow's milk (+) in 11% (-) (-)   (2) (+) significant increase after challenge, (-) no increase *in challenge positive children **particularly in delayed type patients, ***particularly in immediate reactors (2) children with atopic eczema	(1) Kapel et al. 1999 (2) Majamaa et al. 1996
Gastrointestinal Permeability Alteration after cow's milk challenge Urinay Recovery / Test Substances Alteration Ref. polyethylenglycol (PEG) * (1) lactulose/mannitol excretion ratios (+) (3) cellobiose/mannitol excretion ratios (+) (4) Jejunal Biopsy / Test Substances     horseradish peroxidase (HRP) (+)* (2) *significantly changed, (+) increased,  (-) decreased (1) 16 children with CMA (immediate- type), greatest alteration in children with most severe symptoms (2) 15 children with CMA (age of 1-24 months), jejunal transepithelial fluxes (3) 51 children with CMA (skin symptoms and patients with gastrointestinal symptoms), 3 days after challenge (4) 32 children with CMA (age of 3-84 months), 24 hours after challenge	(1) Falth-Magnusson et al. 1986 (2) Heyman et al. 1988 (3) Jalonen 1991 (4) Troncone et al. 1994
Protein / Allergen Absorption Concentrations in blood serum samples Patients human alpha-LA bovine beta-LG Ref. 17 children with CMA (age of 3-78 months)   0.3 to 2 µg/L (in 29%) (1) 20 infants (followed up to 8 months) 3-4 days after birth 31 µg/L at 1 month 6 µg/L at 2 months 2 µg/L at >3 months trace amounts after weaning 1 week 7 µg/L (in 38%) 2 weeks 4 µg/L (in 21%) (2) (1) 24 h after cow's milk challenge (2) median serum levels (per g ALA or BLG given per kg body weight)	(1) Husby et al. 1990 (2) Kuitunen et al. 1994

 

Diagnostic Significance of Tests	References
SPT, Patch Test, RAST Patients / Reference (1) (2) (3) (4) (5) (6) (7) (8) (9) Age (months)   adults 2-36 2-24 50* 62* <24 21* 2-11 a) acute onset 14     36     22   100 b) delayed onset       18     50   76 SPT - positive     a) 67% b) (-) a) (+) 55%   14%       sensitivity   specificity   PPV   NPV         66% 100% 100% 28% 96% 51% 66% 93%     69% 91% 79% 85% Patch Test - positive     a) (-) b) 89% b) (+)     44%       sensitivity   specificity   PPV   NPV                 18% 87% 40% 69% RAST - positive             26%       sensitivity   specificity   PPV   NPV 79% 80% 60-67% 83-100%       100% 30% 57% 100%   85% 38% 61% 71% 58% 88% 70% 81% * mean age, (-) tendency of negative results, (+) association to positive results ------------------- (1) 14 children with immediate reactions to cow's milk, 15 cow's milk tolerant children (2) 21 adults with cow's milk / egg allergy (DBPCFC, 5 different RAST systems) (3) 183 children with CMA and atopic dermatitis (4) 54 children with CMA and atopic dermatitis (5) 430 food allergic children and adolescents (labial food challenge positive) age from 0.2 to 20 years (5) 196 food allergic children and adolescents (54/109 DBPCFC positive) age from 0.6 to 17.9 years, PPV >95% for cow's milk specific IgE >32 kU/L (6) 72 children with CMA (challenge proven) (7) 107 children with atopic dermatitis (47 DBPCFC positive) age from 5 months to 12 years (8) 301 children with suspected CMA (176 DBPCFC positive)	(1) Björkstén et al. 1983 (2) Norgaard et al. 1995 (3) Isolauri & Turjanmaa 1996 (4) Kekki et al. 1997 (5) Rance et al. 1997 (6) Sampson & Ho 1997 (7) Majamaa et al. 1999 (8) Niggemann et al. 1999b (9) Vanto et al. 1999
SPT, IgE and Oral Challenge Diagnostic tests in comparison with oral challenge test in 11 children with CMA (1-15 years of age):   SPT RAST MAST Case History Sensitivity 85% 71% 71%   Specificity   100% 100%   Match 60% 81% 81% 63%	Roger et al. 1994
SPT and DBPCFC Significant differences in SPT (wheal sizes) between cow's milk allergic or tolerant individuals (DBPCFC) (P < 0.001); SPT cut-off values mean diameter 5 mm / surface area of wheal 29 mm2	Eigenmann & Sampson 1998
Skin Tests, RAST, Histamine Release and Lymphocyte Stimulation Positive results with cow's milk (and alpha-CAS*) Test a) b) SPT 57% 0% Patch Test* 33% 0% RAST 59% 33% Histamine Release 55% 17% Lymphocyte Proliferation 77% 17% a) 22 children with CMA (positive challenge test) b) 12 non- milk- allergic controls with atopic dermatitis  Panel of tests detected 21/22 children positive and 5/12 false- positive	(1) Rasanen et al. 1992
Specific Serum IgG Patients / Reference (1) (2) (3) Age 16-58, median 26 years 1-48 (1-72) months   cow's milk specific IgG         NS   NS beta-LG specific IgG         sensitivity   specificity   89% 85%   NS no diagnostic significance ----------------------------------------- (1) 28 adults with CMA (2) 218 healthy children, 205 with CMA, 96 with other (atopic) diseases (commercial betalactotest) (3) 702 infants divided into six groups of different feeding (breast fed, infant formula fed) the shorter the breast feeding period and the earlier cow's milk formula is introduced, the higher the IgG levels	(1) Stoger & Wüthrich 1993 (2) Iacono et al. 1995b (3) Keller et al. 1996
SPT and RAST 41 children  with suspected CMA (age of 3 months to 13 years; mean 2.6 years): 32% SPT positiv, 61% IgE positiv; concordance of SPT and IgE results in 51% (1)	(1) Campbell et al. 1987
Histamine Release, SPT and RAST 26 children  with suspected CMA: 77% positive in oral challenge test; patients with urticaria: high degree of correlation between histamine test, RAST and skin test; patients with gastrointestinal symptoms only a few positive results in histamine test, RAST and skin test (1)	(1) Prahl et al. 1988
Positivity of Open Challenge and DBPCFC in children with history of CMA Patients Open Challenge DBPCFC Ref. 265 children suspected for CMA (mean age 3 months) 56% (n=155) 44% (n=110) (2) a) 16 probable immediate reactors (mean age 37 months)   a) 62.5% with adverse reactions (up to 2 h after milk exposure) (1) b) 53 probable delayed reactors (mean age 17 months)   b) 28.8% with predominantly gastrointestinal symptoms (2h to 6 days after milk exposure) (1)	(1) Baehler et al. 1996 (2) Kaila & Isolauri 1997

Other Features
 

Parameters / Subjects	Outcome	References
Gender of Adults with CMA 34 patients with CMA (aged from 16 to 58 years)	Gender: 91% females, 39% of them experienced first symptoms during or soon after a pregnancy; 47% of patients were nonatopic and showed a monovalent sensitization to cow milk proteins	Stoger & Wüthrich 1993
Adverse vs Allergic Reactions 9 children with "unequivocal symptoms attributable to cow's milk"	CMA in 1 patient, abnormal disaccharide absorption in 3 patients (gastrointestinal and immunoallergic investigations)	Davidson et al. 1976
Cow's Milk Exposure 25 children with CMA (age <1 year)	Exposure to cow's milk formulas (significantly more often than in control group, p < 0.01): 16 during their first week of life 6 before fifth week of life 3 infants not exposed	Stintzing & Zetterstrom 1979
SPT, IgE in Immediate Type CMA 26 (1), 50 (2, 3), and 21 (4) children with IgE mediated acute reactions of CMA	Differentiation of 3 groups by positive SPT to: A) cow's milk only B) cow's milk and whey hydrolysate formula C) cow's milk, whey and CAS hydrolysate formula (1, 2, 3) Significant differences in cow's milk specific serum IgE: A < B < C (1, 2) Significant differences in beta-LG and CAS specific serum IgE: A < C and B < C (1, 2, 3) Most significant difference in intensity scores of IgE- binding to CAS and beta-LG in SDS-PAGE immunoblot: A < C (4)	(1) Schwartz et al. 1989 (2) Schwartz 1991 (3) Schwartz et al. 1991 (4) Amonette et al. 1993

5 Therapy of Cow's Milk Allergy
6 Composition of Cow's Milk
7 Allergens of Cow's Milk
8 Isolation & Preparation