Diete in allergologia:

ancora attuali?

Prof.ssa Erminia Ridolo

Allergologia ed Immunologia clinica

Università di Parma

AGENDA

• Esofagite Eosinofila Primitiva

• Orticaria Cronica Spontanea

• SNAS

• Dermatite Atopica

• Prevenzione delle allergie

Eziopatogenesi

Furuta GT et al. N Engl J Med . 2015 October 22; 373(17): 1640–1648.

Eosinophilic esophagitis (EoE) is a chronic immune/antigen mediated

esophageal inflammatory disease associated with esophageal dysfunction

resulting from severe eosinophil-predominant inflammation

Up to 70% of pediatric and adult EoE

patients have either a history of atopy

or even concurrent allergic disease

EoE children

Sensitizations

to

food-allergens

EoE adults

Sensitizations

to

aeroallergens

Ridolo E et al. AsiaPacAllergy 2012; 2:237-241

Ridolo E. et al Ann Allergy Asthma Immunol. 2011

Jan;106(1):73-4.

3 cases of esophageal eosinophilia in 110 patients treated

with milk OIT at our outpatient clinic.

Sanchez Garcia S et al. JACI

vol.129, n. 4, 2012.

B. D. van Rhijn et al. Allergy 2013

�Pollen and food sensitizations may cause or mantain

esophageal inflammation in EoE patients.

�Aeroallergen sensitization, mostly against components of

grass or tree pollen, or house dust mite, was observed in

74% of the patients.

�Birch pollen (rBet v 1) sensitization with cross-reactivity to

food allergen components was observed in 30 pts (39%).

A role for pathogenesis-related proteins in poly-sensitized allergic patients with eosinophilic

esophagitis: clinical and endoscopic features Ridolo E et al. J Allergy Ther 2014

A role for pathogenesis-related proteins in poly-sensitized allergic patients with eosinophilic

esophagitis: clinical and endoscopic features Ridolo E et al. J Allergy Ther 2014

31 pts

Lucendo a et sl. Guidelines on eosinophilic esophagitis: evidence-based statements and

recommendations for diagnosis and management in children and adultsUnited European Gastroenterology Journal 2017, Vol. 5(3) 335–358

Il ruolo della dieta nell’EoE

Dellon ES et al. Am J Gastroenterol 2013; 108:679-692.

Quale dieta?Elemental diet

Allergy testing-directed

elimination diet

SFED

Arias A et al. Efficacy of Dietary Interventions for Inducing Histologic Remission in Patients With Eosinophilic Esophagitis: A Systematic Review and Meta-analysis. Gastroenterology

2014;146:1639–1648

Groetch et al. J Allergy Clin Immunol Pract 2017;5:312-24

Nutrients in foods commonly eliminated during eosinophilic

esophagitis (EoE) elimination diet therapy

Dieta e orticaria cronica spontanea

10 to 20% of the population will experience an

episode of urticaria at some point in their lifetime

and 0,1% will develop chronic spontaneous

urticaria.

CSU Diagnosis

All subsequent diagnostic steps will depend very much on patient history and on

the nature of the urticaria subtype.

Type I allergy is a rare cause of CSU in patients who present with

daily or almost daily symptoms, but may be considered in CSU

patients with intermittent symptoms.

Pseudoallergic reactions are defined as clinical reactions

whose symptoms resemble allergic reactions without

identifiable immunologic sensitization.

“ …in a subset of patients with chronic urticaria a diet low in pseudoallergens has been proven to be

beneficial in several studies, with response rates observed in more than 55% of patients.

DBPC challenge tests have shown that artificial food additives are not only to blame, with the

majority of reactions being traced back to naturally occuring pseudoallergens in food. ”

Zuberbier T. The Role of Allergens and Pseudoallergens in Urticaria. Journal of Investigative Dermatology Symposium Proceedings, 2001

Estimated median daily salicylate

intakes in the UK population 4.4

mg/day for males and 3.2 mg day

females

Natural salicylates foods

Magerl M. et al. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial. Allergy 2010

For 3 weeks, 140 subjects

with severe-moderate UAS,

followed a pseudoallergen-free diet

and kept a clinical diary for

UAS4 score and DLQI

Prohibited food

Maintz et al. Histamine and histamine intolerance. Am J Clin Nutr 2007

E il ruolo dell’istamina….????

Wagner N et al. JEADV 2017,31,650-655.

Low-histamine diet is a therapeutically useful, simple and cost-free tool to decrease

symptoms and increase quality of life in CsU patients with gastrointestinal involvement.

Further research is needed to understand the role of diamine oxidase.

Wagner N et al. JEADV 2017,31,650-655.

Siebenhaar F et al. JEADV 2016;30, 1774-1777.

CSU due to histamine

intolerance appears to be

rare and cannot be

diagnosed based on the

history.

• A)number of pts with a histamine-positive history is shown in the

yellow column and the number with a histamine-negative history in

the orange column.

• The light green bars; % of pts who had a positive response to diet,

Pink bars: % of pts with a weal response to oral histamine

challenge.

• (b) n° pts with a positive response to diet is shown in the light green

column and the number with a negative response in the darker

green column. The yellow and pink bars show the percentage of

patients within each group who had a histamine-positive history

and a weal response to oral histamine challenge respectively.

• (c) n° pts with a positive weal response to oral histamine

provocation is shown in the pink column and the number with a

negative weal response in the purple column. The yellow and pink

bars show the percentage of patients within each group who had a

histamine-positive history and positive response to diet

respectively.

Il ruolo del Nichel Solfato

Systemic nickel allergy syndrome (SNAS): Cutaneous and extra-

cutaneous symptoms correlated to the ingestion of foods and

beverages containing nickel.

Symptoms include:

- respiratory symptoms (occupational rhinitis and asthma);

- urticaria, angioedema;

- gastrointestinal symptoms (recurrent aphtosis, abdominal bloating and

pain, diarrhoea and/or constipation, nausea and or vomiting, with

endoscopic findings of chronic gastroduodenitis)

- aspecific systemic clinical manifestations (headache, chronic fatigue, post-

prandial dyspnea, cystitis and/or vulvovaginitis, acne and iron deficiency

anaemia).

Ricciardi L. Systemic nickel allergy syndrome: Epidemiological data from fpur italian allergy units. J Neurogastroenterol Motil. 2017 Jan 30;23(1):101-108.

Irritable Bowel Syndrome and Nickel Allergy: What is the

role of the low nickel Diet?

Rizzi A et al. J Neurogastroenterol Motil 2017;23:101-108

Pizzuttelli S. Reply to: update on Systemic Nickel Allergy Syndrome and Diet. Eur Ann Allergy Clin Immunol 2015

• Only cocoa, chocolate, peas and canned foods are

always forbidden

• Six out of 7 diets forbid hazelnuts and peanuts

• Five out of 7 diets proscribe beans, lentils, shellfish,

tea, spinach

• Tomatoes, fish, vegetables are allowed in some

diets, not allowed in others

• Although having low-nickel content, beer, red wine,

herrings, mackerel, tuna, raw tomatoes, onions,

carrots, apples, citrus fruits and other juices are

forbidden in some diets

7 LOW-NICHEL DIETS

Pizzuttelli S. Update on Systemic Nickel Allergy Syndrome and Diet. Eur Ann Allergy Clin Immunol 2015

DOUBTS AND PERPLEXITIES

• Complete elimination of nickel form the diet is impossible (IS

UBIQUITOUS)

• The beneficial effect of a low-nickel diet is not

guaranteed

• Opinions vary about the nickel content wich would determine the

threshold of a low-nickel diet

• There is no unanimity about allowed and forbidden

foods

• Opinions vary about steel pans and kitchen tools, which are not

universally prohibited

• Using tap water is prohibited in some diets, prohibited under

some conditions or allowed in others

• It is not clear how long a low-nickel diet should last

Cutis 2016, Vol 97, 227-232

• 43 articles

• Trials varied in type, duration, and the AD patient populations studied.

• Some level I evidence to support specific exclusion diets in preselected

patients but insufficient evidence for strict elimination diets (diets that are

typically limited to six to eight foods).

• Strict elimination diets and caloric restriction remain discouraging.

• It is important to note that any dietary intervention requires medical

supervision and dietary counseling.

• Risks of elimination diets in children: even limited, such as avoidance of

cows’ milk, present a risk of calorie and nutrient malnutrition.

• Elimination diets may weaken oral allergen tolerance and lead to more

robust allergic reactions.

Lim NR et al. Pediatr Dermatol. 2017 Sep;34(5):516-527

Van Neerven RJJ et al. Nutrition and allergic diseases. Nutrients 2017, 9, 762.

Preventive role of diet in allergic diseases?!?

“Dietary components present in a normal diet may contribute to

prevention of allergies (asthma, rhinitis, dermatitis, atopy and food

allergies), promote the development of allergies (food processing, food

allergy), and more specialized foods can be used for the management or

even the treatment of food allergy.”

Burbank AJ et al. Environmental determinants of allergy and asthma in early life.J Allergy Clin Immunol 2017;140:1-12.

Lifestyle factors can contribute to or diminish microbial diversity. Many aspects of modernity promote dysbiosis.

(Renz et al., J Allergy Clin Immunol 2017;140:24-40)

The first thousand days – intestinal microbiology of early life: establishing a symbiosis

Wopereis H. et al. Pediatric Allergy and Immunology Volume 25, Issue 5, pages 428-438, 5 JUN 2014

• Pioneer species (facultative anaerobic

bacteria) Staphylococcus,

Streptococcus, Enterococcus and

Enterobacter.

After 1-2 weeks: obbligate anaerobes

(Bifidobacterium, Bacteroides, Clostridium,

Eubacterium)

• After introduction of first solid foods (4-6

months of age): decreased level of

Bifidobacteria and gradual diversification

towards adul type species (Bacteroides spp and

Clostridium IV and XIV)

• Healtly adults have a stable microbiota

Immunomodulatory effects of the microbiota in the gut have the potential to decrease allergic inflammatory responses.

- The intestinal mucosa is an immune-

privileged site, which under normal conditions

can tolerate exposure to a huge antigen load

without resulting in an inflammatory response.

- The intestinal microbiota can affect both the

innate and adaptive immune pathways.

- Induces TH1 cell differentiation, which isrequired to establish a balance between TH1 andTH2 immune responses, which corrects the TH2skewing that is thought to occur at birth.

- Expansion of Treg cell subsets in the gut iscritically involved in establishing immunetolerance. Treg cells and immunomodulatorycytokines, such as IL-10 and TGF-b, are involved indecreasing or preventing effector T-cell responsesthat mediate autoimmune or allergic disease.

Mc Loughin RM et a. J Allergy Clin Immunol 2011, 127; 1097-1107.

Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema

compared to healthy children in at-risk for atopic disease.

Nylund et al. BMC Microbiol. 2013 Jan 23;13:12. doi: 10.1186/1471-2180-13-12.

• Composition of the microbiota did

not differ between study groups at

age of 6 months, but was

significantly different at 18 months.

• Healthy children harboured 3

-fold greater amount of

members of Bacteroidetes

(p=0.01).

• Children suffering from

eczema had increased

Clostridium clusters IV and

XIVa, which are typically abundant

in adults.

Effects of probiotics for the treatment of atopic dermatitis: a meta-analysis of randomized controlled trials

Kim et al. Ann Allergy Asthma Immunol 13(2014);9217e226

• The dose of probiotic preparation used in thetrials ranged from 0.3 billion to 20 billion colony-forming units. This might contribute to theheterogeneity among the studies.

• Applying the same dose criteria to variousproducts that consist of different strains might beinappropriate: to find the optimal dose ofprobiotic preparation, a direct head-to-headcomparison study is required.

Despite the conflicting data

obtained from clinical trials,

vitamin D deficiency may

influence the inflammatory

response in the airways.

Hall SC et al. Clinical Therapeutics/Volume 39, Number 5, 2017

• Vit D3 levels are

significantly reduced in

subjects with CU.

• Vit D supplementation

as “add-on” therapy

shows a greater

resolution of CU.

Rasool R et al. WAO J (2015) 8:15.

Miles EA & Calder PC. Nutrients 2017, 9, 784.

Proposed relationship between increased linoleic

acid exposure and increased allergic disease.

Risk of persistent wheeze or asthma in children

according to maternal use of fish oil or

placebo during pregnancy.

• A protective effect on asthma/wheezing

symptoms, but not on allergic rhinitis,

eczema, or atopy.

• During pregnancy might have some

protective effect on asthma/wheeze

symptoms in the offspring only during their first

year of life.

Castro-Rodriguez & Garcia-Marcos. Front. Pediatr. 5:72.

Tanaka T & Takahashi R. Nutrients, 2013, 5, 2128-2143.

Flavonoid intake and risk of chronic diseases

Knekt P et al. Am J Clin Nutr 2002;76:560–8.

CONCLUSIONI

• A tutt’oggi chiare evidenze scientifiche confermano il ruolo delle

diete di eliminazione in caso di esofagite eosinofila primitiva.

• Minor certezze, invece, per Orticaria Cronica Spontanea e

Dermatite atopica.

• Promettenti la dieta mediterranea e diete con supplementazione

di flavonoidi, probiotici e vitamina D per la prevenzione e il

trattamento delle patologie allergiche.

• Dieta di eliminazione di nichel solfato: ???

Grazie per l’attenzione

erminia.ridolo@unipr.it