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Food-provoked eczema: A hypothesis on the possible role of systemic contact allergy to haptens present in both cosmetics and foods
Radoslaw Spiewak
Recommended citation format: Spiewak R: Food-provoked eczema: A hypothesis on the possible role of systemic contact allergy to haptens present in both cosmetics and foods . Estetol Med Kosmetol 2011; 1(1): 35-40.
DOI: http://dx.doi.org/10.14320/EMK.2011.006
Abstract
Patients with eczema frequently associate relapses of their disease with ingestion of particular foods, however, the actual causation by food allergens can be confirmed only in a minority of them. In the present paper, a hypothesis is proposed on the possible causal link between eczema and food in cases not explainable by type I allergy to “classical” food allergens like egg, milk or peanut protein. It is proposed that eczema in such cases may be due to delayed-type allergy to haptens present in food – either natural components, contaminants, or
food additives. A wide range of haptens are used in the production of both food and cosmetics. It is proposed that initial sensitization of the skin to a hapten may follow external exposure (e.g. from skin care products), while relapses in the course of eczema may be due to subsequent oral exposures to the same hapten from food (systemic contact dermatitis). This hypothesis also offers an explanation for cases of photoaggravated eczema by indicating on food haptens with photosensitizing properties. The proposed hypothesis is unifying recent scientific discoveries and clinical observations in the attempt at explaining cases of food-provoked eczema that could not be explained by the present mainstream views on food allergy. Nevertheless, it requires thorough verification through dedicated research aimed specifically at testing the proposed causal relationship between food-provoked eczema and haptens occurring in both cosmetics and foods. If confirmed, appropriate diagnostic methods (e.g. patch test panels with food haptens or specially devised in vitro tests) should be
introduced into routine diagnosis of eczema. Furthermore, results of such studies will provide scientific evidence for possible restrictions on the use of food additives identified as potent sensitizers within the legal scheme of consumer protection policy.
Keywords: eczema, food allergy, food allergens, haptens, food additives, cosmetic ingredients
| Reprint (PDF) | Streszczenie | DOI: 10.14320/EMK.2011.006
Excerpts from the article:
Despite the fact that atopic eczema is associated by
many patients with food allergy, experts have been
aware for a long time that eczema lesions cannot be
readily induced by provocation with food allergens
[1]. Depending on the methodology, hypersensitivity
to food allergens can be confirmed in 10% to 50%
children with eczema [2-4]. In adolescents and adults,
allergies to “classical” food allergens, such as hen’s eggs and cow’s milk are considerably less common and play
a marginal role [3, 5]. Also, “elimination diets” aimed at
curing eczema by excluding various “allergenic foods”
remain ineffective in most cases, and the use of unjustified
dietary regimens in infantile eczema has been criticized
for more than five decades [6]. The simplistic approach
“food allergy causes eczema” seems to be questioned in
many ways, with recent evidence accumulating in favour of the opposite causal relationship, i.e. infantile eczema
being the predisposing condition for a subsequent
development of food allergy, rather than its consequence.
Lack et al. [7] have demonstrated that the use of skin care
products with peanut oil is a strong risk factor for the
development of food allergy to peanuts later in life. In
a mouse model, application of peanut extract or ovalbumin
A on the abraded skin (thus made penetrable to proteins)
both provokes inflammatory skin response with clinical
appearance of delayed-type hypersensitivity (eczema)
and induces production of IgE specific to these allergens
[8]. Similar processes seem probable in humans with
eczema – a disease inextricably linked with disruption
of skin barrier. Putting the above information together,
only in a fraction of eczema patients hypersensitivity
to “classical” protein food allergens can be confirmed
as the cause of their disease. As a matter of fact, food
allergy may be secondary to eczema in many patients.
Allergies to food proteins do not seem to offer a plausible
explanation for most of eczema patients, but many of
them still insist that their skin problems are aggravated
by ingestion of particular foods. In the present article,
a hypothesis is proposed that links eczema provoked by
food with food haptens, rather than “classical” protein
food allergens.
Haptens in food
Haptens are small xenobiotic (exogenous) chemical
molecules with molecular mass below 500 Dalton -
a size that allows them to penetrate through intact
skin [9]. The possibility of hapten penetration through
intestinal mucosa becomes obvious once one realizes
that many oral drugs are also haptens [10]. There are
numerous haptens in food, some of which are natural
components (e.g. nickel, cobalt, vanillin) or contaminants
(pesticides, animal drugs, industrial chemicals), while
others are purposefully added during food processing
(preservatives, emulsifiers, colorants, flavour enhancers,
antioxidants). Haptens are not immunogenic, due to
the fact that they are too small to be recognized by the
immune system’s antibodies or receptors. However,
haptens can form immunogenic complexes with body’s
own proteins. Strong (mainly covalent) chemical bonds
with haptens distort spatial conformation of endogenous
proteins to such extent that these are no longer tolerated
as body’s own structures but instead induce immune
reactions.
Haptens typically cause delayed type hypersensitivity,
which means that symptoms may appear one or even
several days after the ingestion. Under such circumstances,
it is difficult for the patient or even doctor to trace down
the causal link between flares of eczema and ingestion
of a culprit hapten in food. Moreover, various foods may
contain the same haptens, regardless their kind, brand
name or taste. For example, balsam of Peru - a well-known skin sensitizer may be found in chewing gums,
alcoholic drinks, salad dressings, filled chocolates, soft
drinks, and a range of other flavoured products. As
a result, certain haptens may accumulate from various,
seemingly unrelated foods in a hardly traceable way.
This might also lend a possible explanation for patients,
who declare that they can tolerate small amounts of
processed foods, but experience flares of eczema after
indulging themselves with more.
Breastfeeding and haptens
In spite of extensive research, there is still no definitive
proof for the effectiveness of breastfeeding in the
prevention of food allergy and eczema [11]. Sometimes,
flares of eczema in children fed exclusively on mother’s
milk are explained by an alleged passage of allergens into
mother’s milk from food that she ingests. It seems rather
improbable, considering the fact that “classical” food
allergens are proteins and as such undergo hydrolysis
into amino acids in the maternal gastrointestinal
(GI) tract. Nevertheless, some mothers still insist that
they see a connection between their food intake and
child’s eczema flares. The present hypothesis offers
an explanation for this, by indicating on the possibility
of the child being sensitized to haptens in maternal milk.
Drug distribution studies demonstrate that non-protein
drugs may be actively or passively transferred from
mother’s GI tract to breast milk, which most probably
is also true for other haptens [12, 13]. In contrast to
“classical” allergenic proteins, haptens (occurring in
cow milk naturally or as contaminants) would be also
resistant to hydrolytic processes during production of
hypoallergenic milk formulas. It seems, therefore, that
infants may become exposed to food haptens regardless
the way of their feeding.
Photoaggravated eczema
Most patients with eczema respond well to sunlight, and
phototherapy is among relevant therapeutic options for
this disease. In a subgroup of patients, however, sun
exposure causes relapses or aggravations of eczema.
On the ground of the present hypothesis, this might be
explained by the presence of photosensitizing haptens
in food. An example of such photohapten might be
2-phenylphenol, a fungicide with known photosensitizing
properties that is used in the production of citrus fruits.
Citrus fruits are frequently accused of causing skin
problems, therefore the possibility of hypersensitivity
to 2-phenylphenol or other pesticides seems worthwhile
a dedicated study. The underlying processes would
probably be analogous to drug-induced photoallergy or
phototoxicity [14-17].
The breach of tolerance to haptens
Each day we are exposed to dozens of haptens, however,
we remain tolerant of most (if not all) of them, indicating
that the preferred response of the immune system
is tolerance. Immune tolerance is an active process
mediated by specialized subsets of antigen-specific
lymphocytes [18]. The stimuli turning immune tolerance
into hypersensitivity remain unclear, possible factors
of importance with this respect include co-existence
of irritation or inflammation (“danger signals”),
co-exposures, previous exposures, UV-irradiation, site
and the route of primary exposure [19-22]. Evidence
accumulated from numerous animal and human studies
(reviewed recently in [23]) demonstrates that primary
oral exposure to haptens can prevent subsequent
development of contact sensitization through the
skin. However, the surface of human body is exposed
to haptens already in utero, while oral exposure to
highly processed (thus hapten-rich) foods occurs later
in the course of life. This could facilitate the early
development of hypersensitivity to haptens through the
skin, rather than tolerance through oral exposure. With
this regard, another hypothesis - proposed by McFadden
and colleagues [24] that links oral exposure to haptens
with food allergy deserves a mention. According to the
authors, “artificially increased oral exposure to haptens
compete with dietary proteins for the development of
oral tolerance, predisposing to the acquisition of food
protein allergy and representing one driver for the
increasing prevalence of protein allergy and/or atopy”.
In another words, the authors suggest that oral exposure
to food haptens would facilitate the development of
allergy to “classical” protein food allergens, while the
hypothesis outlined in the present article points on
haptens themselves as the possible sensitizers in eczema.
These hypotheses do not necessarily exclude one another,
but rather seem to look at one complex phenomenon
from different perspectives. Furthermore, McFadden
et al. stated that “hapten exposure via other surfaces
such as the skin and airways might also be important
in promoting atopic disease”. In the present hypothesis,
the route of hapten exposure is regarded as a decisive
factors, which is outlined in the following paragraphs.
The possible role of cosmetics in food-related
eczema
The second part of this paper is aimed at explaining
why would intestinal exposure to haptens result in
eczema, i.e. inflammation localized in the skin. Data
on the bioavailability of oral drugs [25] demonstrate
that once absorbed from gastrointestinal (GI) tract into
the blood, haptens may circulate to various organs of
the body, where they can ultimately bind to autologous
proteins and turn them into immunogens. This opens the question, why would haptens absorbed from food
cause eczema and not any other organ’s disease? The
skin is one of the organs richest in immunocompetent
cells, which makes it a good target for allergic reactions.
However, the same is true for the gut or respiratory tract,
yet flares of eczema are rarely accompanied by GI or
respiratory symptoms. One possible explanation could
be that some haptens are capable of forming complexes
only with proteins present exclusively in the skin, e.g.
keratins. This may be true in some cases, but seems
rather insufficient as a general rule. Other, perhaps more
convincing explanation might be the organ specificity of
sensitization processes, rather than haptens themselves.
The central element of acquired immune response are
lymphocytes – cells capable of recognising specific
hapten-protein complexes (HPC) that recruit and
orchestrate inflammatory actions of other cells (e.g.
macrophages, neutrophils, eosinophils, cytotoxic
lymphocytes). There is evidence that naïve lymphocytes
acquire organ specificity at their first encounter with
HPC fitting to their receptors, presented to them by
antigen presenting cells (APC) that migrate into local
lymph nodes from the sites of haptens’ entry. It appears
that next to HPC, signals characteristic of the exposed
organ are transmitted to naïve lymphocytes, which
determines the organ-specificity of daughter effector
and memory cells. These signals could be molecules
carried on the surface of an APC, chemokines or other
factors dissolved in the lymph draining particular
organs. Thus in case of hapten-protein complex
presented by an APC from the skin, in the milieu of
a lymph node flooded with the lymph from the skin, the
antigen specific naïve T cell will ultimately undergo
clonal expansion into skin-homing effector and memory
lymphocytes [26-30]. Some of the daughter lymphocytes
will settle in the skin, while other will circulate in the
blood ready for rapid migration into the skin in case
of re-exposure to the hapten. While the induction of
contact hypersensitivity seems to require the epidermal
route, subsequent elicitations of the disease in already
sensitized subjects may follow systemic exposure to the
hapten, e.g. by oral route. Hapten absorbed from the GI
tract will distribute not only into the skin, but obviously
also to another organs of the body, however, the skin
will be most affected by the inflammatory response due
to predominance of skin-homing effector lymphocytes.
As a matter of fact, cases of eczema provoked by oral
or parenteral exposure to haptens are well-known to
clinicians and are referred to as “hematogenous allergic
contact dermatitis”, “hematogenous contact eczema”,
“systemic contact dermatitis” or “systemic allergic
contact dermatitis” (SACD) [31-35].
In summarising, the occurrence of the same haptens in
cosmetics and food might offer an explanation for cases
of eczema provoked by food that could not be explained
by type I allergy to protein allergens. According to the present hypothesis, such patients may be sensitized to
haptens – initially from cosmetics applied onto the skin
(induction of hypersensitivity), with further relapses of
eczema triggered by the same haptens absorbed from
ingested food (elicitation of hematogenous eczema). As
there are numerous haptens common to cosmetics and
food products (table 1), these processes are very probable
to occur in everyday life and deserve further studies.
Repeated applications of cosmetics onto the skin seem a
very effective way of inducing contact hypersensitivity to haptens, however, in small children the food might
bypass the “cosmetic link”, serving as a primary source
of sensitizing haptens, as it is not unusual in children
to have their food smeared over faces and hands during
their meals.
Future outlook
The hypothesis presented in this paper requires thorough
verification by the means of dedicated studies. One such study should focus on the prevalence of contact
hypersensitivity to food additives among patients with
food-provoked eczema. Such patients should be tested
with an array of haptens used as food additives or
naturally occurring in foods. Cosmetic ingredients with
recognised sensitizing potential that are also used as
food additives (table 1) seem very promising candidates
for such studies, however, other food-specific haptens –
either natural, contaminants or additives – should also
be taken into consideration. After confirming the role
of hypersensitivity to food haptens in food-provoked
eczema, appropriate diagnostic methods (e.g. patch test
panels with food haptens or specially devised in vitro
tests) should be introduced into routine diagnosis of
eczema patients. Furthermore, results of such studies will
provide scientific evidence for possible restrictions on
the use of food additives identified as potent sensitizers
within the legal scheme of consumer protection policy.
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