Six infants were affected with intractable diarrh¬ea and therefore admitted to our ward. That was the birth of allergy, which revolutionized the medical world. Such as Jobs changed our way of living, we insured to sick babies and children a new way of living with allergy, when not escaping it the figures 1-3 show a rare microscopic appearance of the immune cells involved in an oral provocation test. About 40 years ago the whole world lived in the complete ignorance of allergy. We have made the first world diagnosis of allergy and of cow’s milk allergy (CMA) in six parenterally fed babies.
The first world diagnosis of cow’s milk allergy (CMA) has been made in six critically ill children, aged a few months, admitted to the Department of Pediatrics of the Roma University in 1974-75 and recovered in our ward, because afflicted with «intractable» diarrhea and fed par¬enteral¬ly who were first world diagnosed by us. CMA is a severe even perinatal dis¬ease . The infants were par¬enterally fed with all the necessary alimentation. By reviewing their charts, in a shabby chamber which resembled the cottage of the twin’s founders of Rome, so science was highlighted, we read that among their feed¬ing there was the casein . Then the destiny knocked at our door. We looked at our documen¬tation, we were astonished. The casein was the most severe cause of allergy, due to cow’s milk (CM) . It was also the birth of pediatric allergy and immunology science. For a comp¬lete nutrition they were also fed with casein in the ward, therefore the diar¬rhea persisted and aggravated continuously.
In those times (1974-1975) we had a hard job in finding the CM allergens therefore we used initially pure CM in powder so obtaining a huge reaction. Subsequently we were able to confirm the diagnosis with regular allergens. In those heroic times we had a rich collection of cases. Several babies were fed maternal milk (MM), but when they received a diet, the substitute was CM di¬luted 2:1 or 3:1 because of the fat difference between MM and CM . The editor of Annals of Allergy initially refused the paper, with perfect aplomb, because at his eyes it was impossible, thus the paper with the first world diagnosis of CM allergy
(CMA) must wait for publication. If I had sur¬rendered myself to the impossible, I had not the Pediatric Allergy, Asthma and Immunology (in internet) selling seven thousands of copies and two hun¬dreds/a month even in the 4. year of printing  CMA has a very high prevalence, from 0,013 to 45,4%  and severity espe¬cially in the first year of life.
The study was done in 1974-75, in six babies aged 17 days-11 months, three males and three females, who were hospitalized because they were severely ill because diagnosed as suffering from chronic diarrhea with severe malnu¬trition and were therefore fed parenterally. The disease onset varied between a few days and a few weeks, when CM was started, It is important that the babies had not a stool improvement when fed soy milk, therefore some were parenterally fed, some were luckily MM fed. Six infants suffering from chronic diarrhea due to gluten-sensitive enteropa¬thy served as controls for the allergy tests.
The daily parenteral nutrition contained as follows: (Table 1).
We devised for the first time in the world a complete set of
Skin Prick Tests (SPTs)
Appropriate emergency equipment and medications were
available on site. All possible drugs were stopped at least 2
weeks before the application of the SPTs. Six healthy babies
of the same age and sex with the permission of their parents.
Skin testing was done at baseline by the prick method on the
volar surface of the fore-arm by a trained in allergy doctor with
the co-operation of a qualified nurse. The skin was marked
with a ballpoint pen for the allergens to be tested. The babies
were then tested with: histamine hydrochloride (1 mg/ml) as
a positive control and isotonic saline as a negative control. We
con¬tinued with a battery of food allergens, including whole CM
protein, beta-lac¬toglobulin, casein, lactalbumin (Lofarma). The
diagnostic extract of each individual aller¬gen was placed on the
volar surface of the forearm as drops through which the skin was
superficially pricked with a straight pin for one second. A new
pin was used for each SPT and then discarded, and the drop of
the extract was then wiped off about one minute after the prick.
We took for positive only children with a +++ or ++++
reaction, that is a wheal » 3 mm with an area = 7 mm2 (cut-off).
So we considered as positive only the children with a mean wheal
diameter of 3 mm or larger than the negative (saline) control.
A positive (histamine) control was performed to en¬sure the
absence of any antihistamine drug interference.
The statistical analysis was performed using the X2 test.
Results with a p < 0.05 were considered as statistically significant.
At the CM reintroduction, for diagnostic purposes, all babies
presented again with diarrhea, one with a short state of shock
promptly regressed after im¬mediate parenteral treatment.
Hypersensitivity reactions to CM induce an onset of cutaneous,
respiratory, and gastroenteric tract symptoms and we can then
divide by systems the CM credited clinical manifestations. We
studied the clinical manifestations attributed to CMA (Table
3). We then studied the manifestations attributed to CMA on
immunological and nonimmunological basis (Table 4, 4.1).
The infants were diagnosed as having chronic diarrhea due
to CMA if they fulfilled:
Diarrhea persisting more than 3 weeks, with
subsequent failure to thrive,
Positive response to CM elimination diet,
Positive SPTs to casein and lactalbumin,
Exclusion of other causes of infantile chronic diarrhea,
such as cystic fibro¬sis, lactase deficiency, infections,
Before each infant was admitted to the study, parents’
informed consent was obtained In those far times we made
an additional exclusion diagnosis with the primary lactose
intolerance since the children well tolerated MM, whereas they
did not recover by drinking whole CM or a synthetic diet without
casein and deprived of lactose. Gluten intolerance was excluded
since the disturbing symptoms presented themselves previously
from the first gluten eating
All studied babies tested positive to CM and CM allergens,
since they were suffering mostly from gastrointestinal symptoms
(vomiting, diarrhea, as well as failure to thrive, one also showed
lip edema). They were fed a diet containing (Table 5). The meat
was fresh or frozen lamb’s meat, free of both fat and tendons,
cut into small pieces, boiled, minced, and then mixed with the
other components of the diet. In addition we gave two fruits,
bananas and apples. Once obtained the clinical improvement
with this CM-free diet, diarrhea subsided after six days (median)
and infants thrived again after 15 days (median). After clinical
improvement started, we gave also lactose and saccharose,
as well as selected vegetables and additional foods always
excluding CM and foods CM-containing, and veal meat. Gradually
the babies growth improved.
The examination of the peripheral blood, following the
oral provocarion test with CM allergens showed an accelerated
lymphomonocytic response with a great number of lymphocites
already at the second hour after the test. In addition there were
several monocytes showing plasmocytic aspects, immunoblasts
eosinophils and mastocytes, some in a state of degranulation
(Figures 1-3). We have noted that no baby had neither a globose
abdomen anymore, nor foamy stools as seen in celiac disease
The family history for atopy was positive in the six families,
most fathers than mothers suffering from atopy The controls
had negative results, the statistical analysis differed significantly
be¬tween studied babies and controls.
We have done the first world CMA diagnosis in the universe,
a fact that was also the birth of pediatric allergy and immunology
science. We would never have thought it, that the first world
diagnosis of allergy would open such a wide catalogue of CMA
attacks. A new discovery was that allergy; CMA and asthma were
prompted and sustained by hereditary factors . Nwaru et
al.  have studied 994 children. Sensitization to CM allergen
was present in 12% of the children, egg allergen in 9%, wheat
allergen in 5%, and fish aller¬gen in 1%. However the study is
important because it demonstrates the strong association of
additional allergens with disease. Late introduction of potatoes
(4 months), oats (5 months), rye (7 months), wheat (6 months),
meat (5.5 months), fish (8.2 months), and eggs (10.5 months)
was significantly direct¬ly associated with sensitization to food
allergens. Late introduction of potatoes, rye, meat, and fish
was significantly associated with sensitization to any inhalant
In models that included all solid foods that were significantly
related to the end points, eggs, oats, and wheat remained the
most important foods related to sensitization to food allergens,
whereas potatoes and fish were the most important foods
associated with inhalant al¬lergic sensitization . Although
this study in six infants is limited, it is interesting to note that
the female group had a subsidence of diarrhea prior to the male
group We stress that family history was positive in all the six
families (5ß), We have diffused a home-made formula with
lamb meat, rice flour for chil¬dren suffering from food allergy
. The case here reported confirm that CMA in infants can be a
clinical disease of so a high severity that a parenteral nutrition
is required. In our population this was necessary for rather
long periods. The attempts at instituting a soy or synthetic diet
alimentation failed as expected, a baby could be fed MM for two
weeks, and the results were excellent. We suggest to continue
MM in all severely ill infants, where indicated. However the lamb
diet has solved all cases, even in the proportion of seriously
treated babies in this study. To con¬clude, CMA can be the
causative source of much severe diarrhea and dystro¬phy in
infants. The diagnosis can be done on symptoms and on immune
test. No struggle for breastfeeding for allergy prevention is still
working today .
In conclusion, we stress that the first world diagnosis of
allergy and of CMA has revolutionized indeed the world of
al¬lergy and immunology, and perhaps of ge¬netics. It has
since then opened a new window on the allergic-immuno¬logic
plethora of dis¬eased children. As Jobs invented a new way of
living for us, we insured to sick babies and children a new way
of living with allergy, when not turning away. In figures 1-3, it is
shown a quick lymphomonocytic response with a great number
of lymphocites already at the second hour after the provocation
test. In addition there are several monocytes showing
plasmocytic aspects, immunoblasts, eosinophils and basophils.