Food allergies in children with congenital ichthyosis

Relevance. Congenital ichthyosis (CI) is a group of rare skin diseases characterized by impaired keratinization. All forms of CI are associated with impaired skin barrier function, which creates a high risk of transcutaneous sensitization to food allergens and the development of food allergy (FA). Aim: to identify the features of FA in children with various forms of CI.

Materials and methods. An ambispective study was conducted, including 61 children with CI. Patients were divided into 4 groups: Group I – 18 individuals with Netherton syndrome; Group II – 19 children with autosomal recessive CI; Group III – 14 patients with keratinopathic CI; Group IV – 20 children with ichthyosis vulgaris. In all groups, an assessment of allergic history, total immunoglobulin E levels, specific immunoglobulin E levels to 5 allergens was performed, and if necessary, a diagnostic diet and open food challenge were conducted.

Results. Analysis of sIgE levels showed that sensitization to egg white, cow’s milk, and cod was most frequently observed. The highest frequency of elevated sIgE levels was found in children in Groups I, II, and IV. Food allergy occurred in all groups: in Group I – 100.0%, in Group II – 68.42%, in Group III – 42.86%, and in Group IV – 90.0% of cases. Cutaneous-gastrointestinal symptoms of FA predominated in children in Groups I, II, and III, while cutaneous manifestations of FA were more characteristic for children in Group IV. The most common clinically significant food allergens were chicken egg, cow’s milk, gluten-containing products, fish, and nuts.

Conclusions. The obtained data allowed for the assessment of the frequency and features of comorbid FA in children with various forms of CI.

1. Murashkin N.N., Avetisyan K.O., Ivanov R.A., Makarova S.G. Congenital Ichthyosis: Clinical and Genetic Characteristics of the Disease. Current Pediatrics. 2022;21 (5): 362–377. (In Russ.). https://doi.org/10.15690/vsp.v21i5.2459

2. Vahlquist A, Törmä H. Ichthyosis: A Road Model for Skin Research. Acta Derm Venereol. 2020; 100 (7): adv00097. DOI: https://doi.org/10.2340/00015555–3433

3. Sun Q, Burgren N.M, Cheraghlou S, Paller A.S, Larralde M, Bercovitch L, Levinsohn J, et al. The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds. JAMA Dermatol. 2022 Jan 1; 158 (1):16–25. DOI: 10.1001/jamadermatol.2021.4242

4. Egawa G. Pathomechanism of ‘skin-originated’ allergic diseases. Immunological Medicine. 2018; 41 (4), 170–176. https://doi.org/10.1080/25785826.2018.1540257

5. Werfel T, Allam JP, Biedermann T. et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J. Allergy Clin Immunol. 2016; 138 (2): 336–349. DOI: 10.1016/j.jaci.2016.06.010 EDN: XTYENB

6. Zhu TH, Zhu TR, Tran KA. et al. Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation. Br.J. Dermatol. 2018; 179 (3): 570–581. DOI: 10.1111/bjd.16734

7. Brough HA, Lanser BJ, Sindher SB. et al. Early intervention and prevention of allergic diseases. Allergy. 2022; 77 (2): 416–441. DOI: 10.1111/all.15006 EDN: QKTTVK

8. Leung DYM, Berdyshev E, Goleva E. Cutaneous barrier dysfunction in allergic diseases. J. Allergy Clin Immunol. 2020; 145 (6): 1485–1497. DOI: 10.1016/j.jaci.2020.02.021 EDN: RRBRXL

9. Lack G. Epidemiologic risks for food allergy. J. Allergy Clin Immunol. 2008; 121 (6): 1331–1336. DOI: 10.1016/j.jaci.2008.04.032

10. Pearson R.M., Casey L.M., Hughes K.R., Miller S.D., Shea L.D. In vivo reprogramming of immune cells: Technologies for induction of antigen-specific tolerance. Adv. Drug. Deliver Rev. 2017; 114: 240–255. DOI: 10.1016/j.addr.2017.04.005

11. Novik G. A., Zhdanova M. V., Demidova A. S. Epicutaneous sensitization. What do we know? Bulletin of Siberian Medicine. 2021; 20 (4): 180–192. (In Russ.). https://doi.org/10.20538/1682-0363-2021-4-180-192

12. Yamamoto-Hanada K, Kobayashi T, Mikami M, Williams HC, Saito H, Saito-Abe M, Sato M, Irahara M, Miyaji Y, Ishikawa F, Tsuchiya K, Tamagawa-Mineoka R, Takaoka Y, Takemura Y, Sato S, Wakiguchi H, Hoshi M, Natsume O, Yamaide F, Seike M, Ohya Y. PACI Study Collaborators. Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy. J. Allergy Clin Immunol. 2023 Jul; 152 (1): 126–135. DOI: 10.1016/j.jaci.2023.03.008. Epub 2023 Mar 22.

13. Kelleher MM, Dunn-Galvin A, Gray C. et al. Skin barrier impairment at birth predicts food allergy at 2 years of age. J. Allergy Clin Immunol. 2016; 137 (4): 1111–1116.e8. DOI: 10.1016/j.jaci.2015.12.1312

14. Murashkin N.N., Ivanov R.A., Savelova A.A., Fedorov D.V., Opryatin L.A., Ahmad W. Role of the Epidermal Barrier in the Formation of Food Allergies in Children with Genodermatosis. Pediatric pharmacology. 2019; 16 (4): 234–240. (In Russ.). https://doi.org/10.15690/pf.v16i4.2053

15. Guillet G, Guillet MH. Percutaneous sensitization to almond oil in infancy and study of ointments in 27 children with food allergy. Allerg Immunol (Paris). 2000; 32: 309–11.

16. Lack G, Fox D, Northstone K, Golding J. Avon Longitudinal Study of Parents and Children Study Team. Factors associated with the development of peanut allergy in childhood. N Engl. J. Med. 2003 Mar 13; 348 (11): 977–85. DOI: 10.1056/NEJMoa013536. Epub 2003 Mar 10. PMID: 12637607.

17. Boussault P, Leaute-Labreze C, Saubusse E. et al. Oat sensitization in children with atopic dermatitis: prevalence, risks and associated factors. Allergy. 2007; 62: 1251–6. DOI: 10.1111/j.1398-9995.2007.01527.x

18. Galimova A.A. Food Allergy in Children with Congenital Epidermolysis Bullosa: Diss. … Cand. Med. Sci. Moscow, FSBI «National Medical Research Center of Children’s Health», 2025.

19. Astolfi A, Cipriani F, Messelodi D, De Luca M, Indio V, Di Chiara C, Giannetti A, Ricci L, Neri I, Patrizi A, Ricci G, Pession A. Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis. J. Clin Med. 2021 Jan 11; 10 (2): 233. DOI: 10.3390/jcm10020233

20. Stuvel K, Heeringa JJ, Dalm VASH. et al. Comel–Netherton syndrome: a local skin barrier defect in the absence of an underlying systemic immunodeficiency. Allergy. 2020; 75 (7): 1710–1720. DOI: 10.1111/all.14197 EDN: PPVICY

21. Scala E, Condorelli AG, Scala A. et al. IgE sensitization profile in patients with Netherton syndrome. Int Arch Allergy Immunol. 2022; 183 (12): 1291–1296. DOI: 10.1159/000526409 EDN: XHOPUH

22. Barbati F, Giovannini M, Oranges T. et al. Netherton syndrome in children: management and future perspective. Front Pediatr. 2021; 9: 645259. DOI: 10.3389/fped.2021.645259 EDN: JCFTWU

23. Kalb B, Marenholz I, Jeanrenaud ACSN, Meixner L, Arnau-Soler A, Rosillo-Salazar OD, Ghauri A, Cibin P, Blümchen K, Schlags R, Hansen G, Seidenberg J, Keil T, Lau S, Niggemann B, Beyer K, Lee YA. Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy. J. Allergy Clin Immunol. 2022 Nov; 150 (5): 1125–1134. DOI: 10.1016/j.jaci.2022.05.018

24. Brown SJ, Asai Y, Cordell HJ. et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J. Allergy Clin Immunol. 2011; 127: 661–7. DOI: 10.1016/j.jaci.2011.01.031

25. Namazova-Baranova LS. Allergiya u detei: ot teorii k praktike. Moscow: The Union of Pediatricians of Russia, 2010–2011. 668 p.

26. Food Allergy in Children and Adolescents: [Monograph] / S.G. Makarova, I.I. Balabolkin, A.P. Fisenko. Moscow: FSAI «National Medical Research Center for Children’s Health» of the Ministry of Health of Russia, 2021. 288 p. 27. Clinical Guidelines «Food Allergy» dated 23.12.2026. https://medpoint.pro/article/pishchevaya-allergiya-2166

27. Molina-Infante J, Arias Á, Alcedo J, Garcia-Romero R, Casabona-Frances S, Prieto-Garcia A, Modolell I, Gonzalez-Cordero PL, Perez-Martinez I, Martin-Lorente JL, Guarner-Argente C, Masiques ML, Vila-Miravet V, Garcia-Puig R, Savarino E, Sanchez-Vegazo CT, Santander C, Lucendo AJ. Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study. J. Allergy Clin Immunol. 2018 Apr; 141 (4): 1365–1372. DOI: 10.1016/j.jaci.2017.08.038