Pseudoallergen-Free and Low-Histamine Diet in Adolescents With Chronic Spontaneous Urticaria

Official title

Clinical Response to a Histamine- and Pseudoallergen-Restricted Diet in Patients With Chronic Urticaria

Overview

The goal of this clinical trial is to learn whether a histamine- and pseudoallergen-restricted diet can help reduce symptoms in people with chronic urticaria. It will also learn whether this diet changes the need for urticaria medication. The main questions it aims to answer are: Does the diet lower urticaria activity, including hives and itching? Does the diet improve disease control and quality of life? Does the diet change the need for urticaria medication? Which clinical or laboratory factors may affect response to the diet? There is no comparison group. Researchers will compare participants' symptoms before and after the diet. Participants will: Follow a structured histamine- and pseudoallergen-restricted diet Continue their usual urticaria treatment as recommended by their doctor Record or report their urticaria symptoms during follow-up Visit the clinic for assessment of symptoms, disease control, quality of life, medication use, and laboratory findings.

Detailed description

Chronic spontaneous urticaria in children is a heterogeneous condition characterized by recurrent wheals, angioedema, or both for more than six weeks without a consistent external trigger. Although second-generation H1-antihistamines are the mainstay of treatment, disease activity may persist in some children despite standard care.

Dietary factors, including histamine-rich foods, histamine-releasing foods, and pseudoallergens such as selected additives, preservatives, colorants, and naturally occurring food components, have been proposed as potential aggravating factors in a subset of patients. However, the clinical value of dietary restriction in pediatric chronic spontaneous urticaria remains uncertain, and better evidence is needed to determine whether a time-limited dietary approach provides additional benefit.

This randomized controlled study will evaluate a structured low-histamine and pseudoallergen-free diet as an adjunct to standard guideline-based care in children with chronic spontaneous urticaria. The comparator group will receive standard care with general age-appropriate healthy eating advice, without specific restriction of histamine-rich or pseudoallergen-containing foods during the primary comparison period.

All participants will continue to receive standard clinical care according to current urticaria management principles. Antihistamine treatment will be permitted according to clinical need. The study will also explore whether baseline clinical and laboratory characteristics, including autologous serum skin test status and routine inflammatory markers, are associated with response to the dietary intervention.

Because this is a pediatric dietary study, the dietary intervention will be standardized, time-limited, and implemented with parental guidance. Unnecessary prolonged dietary restriction will be avoided.

Interventions

• Behavioral Intervention Name: Low-histamine and pseudoallergen-free diet
  Participants assigned to the intervention group will receive a structured low-histamine and pseudoallergen-free diet for 4 weeks in addition to standard guideline-based clinical care. The diet will restrict histamine-rich foods, foods considered to promote histamine release, and foods containing common pseudoallergen sources such as selected additives, preservatives, colorants, and naturally occurring pseudoallergen-rich foods. Antihistamine treatment will be permitted according to clinical need
• Behavioral General healthy eating advice
  Participants assigned to the control group will receive standard guideline-based clinical care together with general age-appropriate healthy eating advice. No specific restriction of histamine-rich foods, histamine-releasing foods, or pseudoallergen-containing foods will be recommended during the primary 4-week comparison period. Antihistamine treatment will be permitted according to clinical need.

Primary outcome measures

• Change in weekly urticaria activity score [Time frame: Baseline to week 4]
• Change in urticaria control test score [Time frame: Baseline to week 4]

Secondary outcome measures (4)

• Change in dermatology quality-of-life score [Time frame: Baseline to week 4]
• Change in antihistamine requirement [Time frame: Baseline to week 4]
• Proportion of participants achieving clinical response [Time frame: Baseline to week 4]
• Dietary adherence [Time frame: Basaline to week 4.]

Eligibility criteria

IInclusion Criteria:

Children aged 1 to 18 years Diagnosis of chronic spontaneous urticaria Disease duration of at least 6 weeks Presence of active urticaria symptoms at enrollment Ability of the child and/or parent/caregiver to complete symptom and diet follow-up forms Ability and willingness of the family to follow the assigned dietary recommendation Written informed consent from parent or legal guardian Assent from the child when applicable

Exclusion criteria

Pure chronic inducible urticaria Urticaria secondary to an identified trigger IgE-mediated food allergy requiring a specific elimination diet Active infection or parasitic disease Oral corticosteroid use within the previous 4 weeks Current or recent biological treatment for chronic urticaria Coeliac disease Inflammatory bowel disease Known systemic mast cell disease Severe chronic systemic disease affecting diet, growth, or follow-up Significant malnutrition or a medical condition requiring a special diet Pregnancy or lactation in postmenarchal adolescents Inability or unwillingness of the child or family to adhere to the assigned dietary recommendation Incomplete follow-up data

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 1 center

• Istanbul University, Istanbul Faculty of Medicine, Department of Pediatric Allergy and Imm — Istanbul

Publications

• Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, Baker D, Ballmer-Weber B, Bangert C, Ben-Shoshan M, Bernstein JA, Bindslev-Jensen C, Brockow K, Brzoza Z, Chong Neto HJ, Church MK, Criado PR, Danilycheva IV, Dressler C, Ensina LF, Fonacier L, Gaskins M, Gaspar K, Gelincik A, Gimenez-Arnau A, Godse K, Goncalo M, Grattan C, Grosber M, Hamelmann E, Hebert J, Hide M, Kaplan A, Kapp A, K PMID 34536239
• Weller K, Groffik A, Church MK, Hawro T, Krause K, Metz M, Martus P, Casale TB, Staubach P, Maurer M. Development and validation of the Urticaria Control Test: a patient-reported outcome instrument for assessing urticaria control. J Allergy Clin Immunol. 2014 May;133(5):1365-72, 1372.e1-6. doi: 10.1016/j.jaci.2013.12.1076. Epub 2014 Feb 9. PMID 24522090
• Mlynek A, Zalewska-Janowska A, Martus P, Staubach P, Zuberbier T, Maurer M. How to assess disease activity in patients with chronic urticaria? Allergy. 2008 Jun;63(6):777-80. doi: 10.1111/j.1398-9995.2008.01726.x. PMID 18445192
• Magerl M, Pisarevskaja D, Scheufele R, Zuberbier T, Maurer M. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial. Allergy. 2010 Jan;65(1):78-83. doi: 10.1111/j.1398-9995.2009.02130.x. Epub 2009 Oct 1. PMID 19796222
• Kapat A, Murmu R, Mandal S, Biswas K, Sarma N, Bala AK. Effect of Dietary Intervention in Paediatric Patients with Chronic Spontaneous Urticaria: Open Labelled Randomised Controlled Trial. Maedica (Bucur). 2025 Jun;20(2):275-282. doi: 10.26574/maedica.2025.20.2.275. PMID 40880715

Identifiers

NCT: NCT07632040 · ASST-PAF-LH-CSU-2025-3729877 · 2025-3729877

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗