Food Allergy-Associated Cutaneous Manifestations in Children: A Narrative Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

It's a good work and interesting .

I don't agree with you using epinephrine for allergic angioedema. We use corticosteroid and antihistamine. Epinephrine for anaphylaxis.

I agree with you of the importance of working in multidisciplinary team (dermatologist, allergologist, gastroenterologist and also other like lab, pathological anatomy).

You don't write about biologic therapy nor immunotherapy (AIT) and today I think these therapies are very important.

Author Response

Comment 1: "I don't agree with you using epinephrine for allergic angioedema. We use corticosteroid and antihistamine. Epinephrine for anaphylaxis."

Response 1: Thank you for your comment. After reviewing the section and associated reference, we agree with your comment and a correction has been made. The manuscript originally had used the treatment for angioedema in the context of anaphylaxis, which was unclear. The manuscript has been updated to include the correct treatment of angioedema with and without the context of anaphylaxis. Page 4 line 118-121: "If anaphylactic angioedema is suspected, first line treatment is intramuscular (IM) epinephrine, followed by H1 and H2 antihistamines, and corticosteroids. For angioedema alone, corticosteroids and antihistamines alone are to be used; epinephrine is an escalation for anaphylaxis [8]."

 

Comment 2: "You don't write about biologic therapy nor immunotherapy (AIT) and today I think these therapies are very important."

Response 2: Thank you for your comment. We agree with your perspective. A new paragraph has been added under "4.2 Management Strategies," page 7 lines 273-292, addressing this. The table has also been updated accordingly. The following text has been added: "In recent years, biologic therapies and allergen immunotherapy (AIT) have emerged as promising adjuncts in the management of pediatric food allergies, particularly in cases of severe IgE-mediated reactions or coexisting atopic dermatitis. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit and inhibiting IL-4 and IL-13 signaling, has been FDA-approved for children aged 6 months and older with moderate-to-severe atopic dermatitis. Studies have shown that dupilumab not only improves eczema but may also modulate the allergic immune response, potentially reducing food allergen sensitivity over time [34]. On the other hand, AIT, including oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT), involves gradual exposure to increasing doses of an allergen to induce desensitization. In a phase 3 trial of AR101, a standardized peanut protein formulation, participants who received OIT were significantly more likely to tolerate peanut exposure compared to placebo [35]. Though still under investigation for long-term efficacy and safety, peanut OIT has been approved for children aged 4 to 17 years. Omalizumab, an anti-IgE monoclonal antibody, is another biologic that has been investigated for its role in facilitating oral immunotherapy (OIT) by decreasing the risk of anaphylaxis during food reintroduction. FDA-approved in 2024 for food allergy in children, omalizumab has shown promise in clinical trials as a co-therapy with peanut OIT [36]. Even so, OIT carries a risk of adverse reactions and requires close monitoring by allergy specialists. Overall, these therapies represent a shift from strict avoidance toward immune modulation, offering hope for more durable tolerance in select patients."

Reviewer 2 Report

Comments and Suggestions for Authors

1. Rename the title to include : A Narrative Review
2. The Results was a discussion
3. Show your manuscript flow chart in the Results
4. Reviews often list all the manuscripts used in the review

Author Response

Comment 1: "Rename the title to include : A Narrative Review"

Response 1: Thank you for your comment and we agree. The title has been updated to include ": A Narrative Review"

Comment 2: "The Results was a discussion"

Response 2: Thank you for this feedback. We have revised the section to ensure that it is strictly focused on presenting the findings of the reviewed literature, without interpretation or discussion. Any interpretive comments have been moved to the Discussion section to maintain clarity and structural integrity. Please see changes to section 3.2, 4.1, and 4.2 for details.

Comment 3: "Show your manuscript flow chart in the Results"

Response 3: Thank you for your suggestion. As this manuscript is a narrative review rather than a systematic review, a PRISMA-style flowchart was not included. Our selection of references was based on relevance to the topic rather than a formal screening process.

Comment 4: "Reviews often list all the manuscripts used in the review"

Response 4: We appreciate this recommendation. As this was a narrative review rather than a systematic review, we have selectively cited key manuscripts relevant to our discussion of food allergy–associated cutaneous manifestations in children. All manuscripts used in the review have been cited in the references.

Reviewer 3 Report

Comments and Suggestions for Authors

The article is a general review of food allergies, with little focus on skin symptoms as stated in the title.

Specific comments.

1) There are no new findings describing IgE-dependent food allergy or atopic dermatitis.

2)Foods associated with IgE-dependent food allergies and atopic dermatitis vary by age and country, but no mention of this.

3)The differences in skin symptoms between atopic dermatitis with and without food allergy involvement should be discussed.

4) The cutaneous symptoms of FPIES, FPIAP, and eosinophilic esophagitis should be discussed. If there are no symptoms associated with FPIES, FPIAP, and eosinophilic esophagitis, the section of 3.3 and Table 1 are meaningless and out of scoop of this manuscript.

 

Author Response

Comment 1) There are no new findings describing IgE-dependent food allergy or atopic dermatitis.

Response 1: Thank you for your comment. We agree with this statement. There are no new findings in this manuscript because it is a review of current data and literature. No new data or findings are being reported.

Comment 2)Foods associated with IgE-dependent food allergies and atopic dermatitis vary by age and country, but no mention of this.

Response 2: Thank you for your comment. We agree with your suggestion. We have taken action to address this by including a new paragraph on this matter under "4.2 Management Strategies" Page 6, lines 239-247.

Comment 3)The differences in skin symptoms between atopic dermatitis with and without food allergy involvement should be discussed.

Response 3: Thank you for your comment. We agree with your suggestion. We have added new text addressing this under "3.2 Atopic Dermatitis and Food Allergy" Page 4 lines 134-140.

Comment 4) The cutaneous symptoms of FPIES, FPIAP, and eosinophilic esophagitis should be discussed. If there are no symptoms associated with FPIES, FPIAP, and eosinophilic esophagitis, the section of 3.3 and Table 1 are meaningless and out of scoop of this manuscript.

Response 4: Thank you for your comment. We agree that it is important to discuss the cutaneous symptoms of FPIES, FPIAP, and eosinophilic esophagitis. These have already been discussed in the manuscript under "3.3 Non-IgE Mediated Allergies and their Presentations". We have highlighted the answers to your comment in green. They are found on page 4 and 5 lines 150- 154, 162-163, and 171-172.

Reviewer 4 Report

Comments and Suggestions for Authors

The interpretations made by the authors are interesting, but I believe that a number of clarifications need to be made:

- Discussions and interpretations should also be correlated with aspects related to the quality of the ingested food, the degree of processing, the specificity of the raw material, the predisposition of certain food categories to generate a series of problems that cause the appearance of allergies, but also to the genetic predisposition of children to develop some complications depending on food consumption.

- The composition of foods should be more clearly linked to the subsequent manifestation of food allergies that may occur in children.

Author Response

Comment 1: Discussions and interpretations should also be correlated with aspects related to the quality of the ingested food, the degree of processing, the specificity of the raw material, the predisposition of certain food categories to generate a series of problems that cause the appearance of allergies, but also to the genetic predisposition of children to develop some complications depending on food consumption.

Response 1: Thank you for your comment. We agree with your suggestions that these are very interesting topics to explore. Unfortunately, there is very limited data on them. We have added some text addressing the route and form of allergen exposure, but the molecular and genetic aspect of allergens falls outside of the scope of this paper. We have added this discussion to the "5. Conclusions and Future Directions" of the manuscript. Please see page 8 and 9 lines 319 to 332. 

Comment 2: The composition of foods should be more clearly linked to the subsequent manifestation of food allergies that may occur in children.

Response 2: Thank you for your comment. We agree that the composition of foods is an interesting aspect to explore in food allergies. This review focuses on foods generally causing cutaneous symptoms in children. We have adjusted the future directions section to address that it would be useful to differentiate between organic vs GMO and farm-raised vs wild-caught foods in the context of allergy. Please see page 9 lines 328 to 332. 

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Good revisions

Author Response

We appreciate the reviewer’s positive feedback on the revisions.

Reviewer 3 Report

Comments and Suggestions for Authors

Even in a review article, it is necessary to include some new information, propose new concepts, or offer new interpretations. Unfortunately, no new information has been added to the revised manuscript.

If pallor is a skin symptom with high specificity in distinguishing non-IgE-dependent food allergies from other diseases, it is worth considering. However, pallor does not have high specificity. It is unreasonable to emphasize pallor as a skin symptom in non-IgE-dependent food allergies.

Author Response

Comment 1: “Even in a review article, it is necessary to include some new information, propose new concepts, or offer new interpretations. Unfortunately, no new information has been added to the revised manuscript.”

Response 1:

We appreciate the reviewer’s comment. While this narrative review does not present newly generated primary data, it offers new synthesis and interpretation in an area that has not been consolidated for clinicians before. To our knowledge, no prior review has focused exclusively on the cutaneous manifestations of food allergy in the pediatric population, addressing an important gap for dermatologists, allergists, pediatricians, and gastroenterologists.

In addition, the revised manuscript integrates emerging management strategies from a dermatologic perspective by combining data on allergen immunotherapy and relevant biologics (dupilumab, omalizumab). This highlights practical implications for skin disease and safety considerations that have not been collectively discussed for pediatric food allergy skin presentations.

Finally, the Future Directions section proposes targeted ideas that could stimulate new research. These include refining diagnostic criteria and developing biomarkers to distinguish sensitization from true clinical allergy in the context of atopic dermatitis, examining how route and form of allergen exposure influence sensitization risk, and exploring whether food composition or sourcing affects allergy development and cutaneous expression. We believe these proposals are novel within this niche and provide a foundation for further investigation.

 

Comment 2: “If pallor is a skin symptom with high specificity in distinguishing non-IgE-dependent food allergies from other diseases, it is worth considering. However, pallor does not have high specificity. It is unreasonable to emphasize pallor as a skin symptom in non-IgE-dependent food allergies.”

Response 2:

We appreciate the reviewer’s comment. We have revised the discussion of skin findings in non-IgE-mediated food allergy (Section 4.1) to note that cutaneous changes are less consistent and, to our knowledge, there are no highly specific skin findings unique to these conditions. We have also specified that reported nonspecific features include pallor, mottling, perioral erythema, transient maculopapular eruptions, and, less commonly, diaphoresis. In the appropriate clinical context, these findings may help support suspicion for a non-IgE-mediated mechanism.

These changes appear in the Discussion section to highlight their diagnostic relevance while avoiding repetition from the Results. This placement ensures the discussion is framed within the broader clinical context.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors have improved the manuscript by providing the requested additions and clarifications.

Author Response

We appreciate the reviewer’s positive feedback on the revisions.