The Potential Link Between Food Allergies and the Insurgence of Allergic and Rheumatoid Arthritis: A Systematic Review

Abstract

Introduction: The potential role of food hypersensitivity in the insurgence of inflammatory activity in arthritis such as Rheumatoid Arthritis (RA) has received intermittent attention, also supported by theoretical links involving mucosal immunity, mast-cell activation, and microbiome–immune interactions. Despite biological plausibility, the clinical significance of dietary antigens in RA remains uncertain. Methods: A systematic review was conducted following the PRISMA guidelines. Searches using PubMed, Scopus, and Web of Science identified studies exploring dietary interventions or food hypersensitivity in RA. Eligible articles included clinical trials, case reports, and observational studies, in English or Italian, up to the 10 December 2025. Data extraction and quality assessment were performed using the Newcastle–Ottawa Scale. Results: Eight studies met the inclusion criteria. Findings indicate that elimination or elemental diets occasionally yielded subjective improvements—such as a reduction in pain, morning stiffness, and functional improvements—yet objective inflammatory markers rarely changed. Small, highly selected, cohorts demonstrated immuno-histological alterations, including reduced mast-cell density, while long-term diets (e.g., gluten-free or vegan) have reduced specific IgG levels without altering radiographic progression. Conclusions: Evidence suggests that dietary interventions may offer symptomatic relief only in a minority of RA patients. Due to methodological constraints, inconsistent outcomes, and limited applicability to contemporary treatments, dietary approaches need further exploration and investigation. Rigorous trials in modern cohorts are warranted to clarify whether food hypersensitivity meaningfully influences RA pathophysiology.

1. Introduction

Over the past few decades, increasing attention has been paid to the link between immunological activation, musculoskeletal disease, and dietary variables. Arthritis has been defined as “an acute or chronic inflammation of the joints”, however nowadays there are many different types of arthritis which vary based on the mechanism of aetiophatology [1]. The concept of “allergic arthritis” is the inflammation which occurs due to a hypersensitivity reaction after an exposure to antigens, in this case, triggered by food antigens. Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting approximately 0.5–1% of the global population [2]. Allergic arthritis is not officially recognized as a rheumatologic entity; however, evidence suggests that the immune system may react to certain food antigens in ways that modify systemic inflammation, mucosal immunity and, possibly, joint homeostasis in susceptible individuals [3], particularly in the context of customized or precision nutrition methods for chronic inflammatory disorders, for example in Rheumatoid Arthritis (RA). Recent developments in immunology, mucosal biology, and microbiome science have sparked a resurgence of interest in this topic.

This adverse reaction is broadly defined as “food hypersensitivity” and it includes food allergies, immunologic and non-immunological reactions which can cause a wide range of symptoms or exacerbate symptoms in chronic inflammatory diseases like RA [4]. According to the European Academy of Allergy & Clinical Immunology (EAACI), food hypersensitivity can be classified in two different arms which are food allergy (immune mediated) and food intolerance (non-immune mediated). Food allergy can be sub-classified as IgE mediated, non-IgE mediated or mixed (IgE and non-IgE mediated). On the other hand, food intolerance is a non-immune mediated reaction which could be, for example, enzymatic deficiencies, toxic or pharmacological [5,6].

In this regard, in 2014 a very extensive systematic review was published by the EAACI in order to estimate the prevalence of food allergies in Europe, and in an updated systematic review by Spolidoro et al. this prevalence was shown to have risen from 2.6% in 2000–2012 to 3.5% in 2012–2021 [7,8]. Santos AF et al. in another study mentions that the prevalence, globally, is estimated to be as high as 10% and is said to be increasing over the years [9,10,11].

Long regarded as central effector cells in IgE-mediated allergic reactions, mast cells are becoming important players in inflammatory processes that go beyond traditional allergies. By releasing histamine, cytokines, proteases, lipid mediators, and other bioactive chemicals that affect both innate and adaptive immunity, mast cells have been shown to be able to coordinate a wide range of immunological responses [12,13]. Mast cells contribute to the chronicity of inflammatory arthritides by taking part in angiogenesis, cartilage degradation, and cytokine amplification loops within the synovial milieu [14]. These findings imply that different inflammatory patterns in joint tissue may occur in people with increased mast-cell reactivity or allergic propensity.

The intestinal barrier plays a crucial role in determining systemic immune responses, as demonstrated by concurrent developments in mucosal immunology. To stop dietary antigens, microbial products, and other luminal materials from moving into the systemic circulation, the integrity of the epithelial tight junctions is essential. Increased antigen exposure and systemic immune activation can result from disruption of this barrier, often known as “leaky gut”, which can be caused by genetic, environmental, nutritional, and inflammatory factors [15]. Increased intestinal permeability is linked to a number of autoimmune and inflammatory conditions, such as RA and spondyloarthropathies, according to both experimental and clinical research [16]. This implies that dietary factors may indirectly cause joint inflammation in certain people by changing the integrity of the mucosa or increasing the antigenic load.

Another important link between food and systemic immunity is gut microbiome. Nutrient metabolism, epithelial barrier function, and immune differentiation, specifically, the equilibrium between proinflammatory and regulatory T-cell populations, are all regulated by symbiotic microbes [17]. Rheumatoid arthritis (RA) and other autoimmune disorders have been repeatedly associated with dysbiosis, an imbalance or reduction in microbial diversity [18,19,20]. The composition of microbiota is significantly influenced by dietary habits, and even minute changes in microbial ecology can affect how the host immune system reacts to food antigens. Therefore, a possible molecular basis for food-related modulation of joint symptoms is provided by the interaction between diet, microbiota, and systemic inflammation.

Adverse food reactions and food allergies themselves show significant immunological variability. Food-induced inflammation is largely caused by non-IgE immunologic pathways, such as T-cell-mediated hypersensitivity, innate immune activation, or mixed mechanisms, even though IgE-mediated reactions are the most well-known [10,21,22]. Food antigens may activate pattern-recognition receptors, resulting in cytokine production and immunological amplification even in the absence of classical allergy, according to recent discoveries about innate immune recognition of dietary proteins [23,24]. These pathways offer a conceptual link between systemic inflammatory symptoms and dietary exposures.

The idea that nutrition affects inflammatory rheumatic disorders is further supported by research on more general dietary patterns. Due to their combined impact on metabolic pathways, microbiome composition, and low-grade inflammation, Mediterranean, plant-based, and anti-inflammatory dietary patterns have been linked to improvements in rheumatoid arthritis pain, fatigue, and inflammatory biomarkers [25,26,27,28,29]. These studies support the idea that the immune system is sensitive to dietary cues and that diet may play a modifiable role in musculoskeletal inflammation, even though they do not directly address food allergies.

The possibility of food-triggered joint discomfort is further supported by autoimmune disorders associated with dietary antigens. For instance, celiac disease demonstrates how a particular food antigen (gluten) can cause extraintestinal symptoms, musculoskeletal problems, and systemic inflammation; many of these symptoms ameliorate with rigorous antigen avoidance [30,31,32]. These conditions demonstrate how food antigens can cause systemic immune reactions that are relevant to rheumatology even in the absence of traditional IgE-mediated allergies.

Lastly, observational epidemiology points to intricate connections between autoimmune rheumatic diseases and allergy diseases. Although results are varied and probably impacted by common genetic or environmental factors, a number of studies suggest that people with atopy may have a distinct immunological milieu or an altered risk of developing rheumatoid arthritis [3,33,34]. These correlations highlight the wider interaction between hypersensitivity, immune modulation, and chronic inflammatory disease, even though they do not prove a direct link between food allergies and arthritis.

When combined, these discoveries offer a compelling scientific justification for examining the relationship between immunological hypersensitivity, joint inflammation, and food antigens. Mechanistic developments in mast-cell biology, intestinal permeability, and microbiome studies increasingly support the possibility of food-induced arthritis, even though it is still a rare and poorly understood event. Therefore, this review aims to elucidate possible mechanisms connecting dietary antigens to joint inflammation, contextualize the clinical and molecular information that is now available, and also suggest future research options in this developing field.

2. Materials and Methods

2.1. Selection Protocol and Search Strategy

In conducting the current systematic review, the Preferred Reporting Methodology for Systematic Reviews and Meta-Analyses (PRISMA) was followed. PRISMA is a 27 step checklist that, when followed, ensures completeness, transparency and reproducibility of systematic reviews, as it minimizes selection bias [34,35].

Data was obtained by searching databases (PubMed, Scopus, Web of Science) using the terms “food hypersensitivity”, “food intolerance”, “diet”, “elimination”, “arthritis”, and “rheumatoid arthritis” [36].

2.2. Inclusion and Exclusion Criteria for the Study

Additionally, each article identified in the previous search was then screened, first based on the title and abstract, and then based on the full text. Subsequently, each author (L.C. and M.S.) chose the articles independently. The same authors (L.C. and M.S.) reviewed each article in an independent manner. If any issues, uncertainties, or inconsistencies were found, the authors agreed unanimously after thorough discussion. All studies that assessed people with food allergies and arthritis were considered eligible. Only English- or Italian-language articles, published up until the 10 December 2025, have been included. This includes case reports, clinical trials, and randomized controlled trials with original dates.

2.3. Data Extraction and Quality Assessment

Subsequently, for each article identified, an initial screening was carried out based on the abstract. All necessary information was then extracted from each of those articles considered suitable for inclusion after carrying out a thorough analysis.

This includes details regarding the author, year, nation, participants, intervention or exposure, key findings, and limitations for each of the eligible studies.

Data was then organized using a variety of assessment and intervention techniques.

The quality assessment was then carried out using the Newcastle–Ottawa Quality Evaluation Scale (NOS). The NOS evaluates observational studies using a set of questions, and each study can get up to nine points in three distinct categories. The first area, “SELECT” (4 points), which considered the study group selection, the sample size, the responder profile, and the clarity of the major risk factors.

The second category, “compatativity,” includes the comparability of the different result groups as well as the existence or lack of confounding variables (2 points). Section 3 and Section 5, “results” (3 points), examined whether exposure and outcome verification were assessed in a straightforward manner, and whether statistical testing, when used, was appropriate. After the scores were added up, the final score was categorized as “good” if it was above 7, “fair” if it was between 5 and 7, or “poor” if it was below 5 [37].

3. Results

A total of 446 records were found while searching the databases (PubMed, Scopus, Web of Science). Screening the reference lists yielded an additional 22 articles, bringing the total to 468 items. After removing all duplicates, only 198 articles remained. These were then screened based on their abstract and title. Of these, 142 were discarded due to being deemed irrelevant. Subsequently, the full-texts of the remaining 56 papers were then assessed for eligibility. Of these, 48 were excluded due to factors such as inadequate data, non-human study designs, or irrelevance to the topic. Eight papers were included in the qualitative synthesis as they satisfied all the inclusion criteria (Figure 1).

All findings are included in

Table 1. Results and Findings.

Author, Country, Year	Study Type	Participants	Intervention/Exposure	Main Findings	Limitations and Quality
Panush et al., USA, 1986 [36]	Prospective blind observational study	52 yr; woman with exacerbation of arthritis with milk, meat and beans	Fasting (3 days) or taking Vivonex (2 days), no morning stiffness, tender joint score of 1, swollen joint score of 0, and assessments of 100%	On her normal diet for 6 days, she averaged 30 min of morning stiffness, 9 tender joints, 3 swollen joints, 87% subjective assessment (100% = best possible), and 89% examiner assessment. These data relate to symptomatic exacerbation of inflammatory arthritis with immunologic hypersensitivity to milk. Non–IgE-mediated immune mechanism linking milk ingestion to inflammatory arthritis flares.	Very small sample. Fair quality
Pacor et al., Italy, 2001 [37]	Case reports	34 yr, woman with seronegative arthritis and tenosynovitis; 29 yr man with seronegative spondylitis; Both had a previous history of food allergy (milk and wheat)	IgE-mediated food allergy diagnosis; elimination diet; followed by open food challenge; subsequently confirmed by repeated double-blind placebo-controlled food challenge tests	Joint symptoms improved or resolved during elimination diet	Only 2 cases; cannot generalize. Fair quality
Felder et al., Swiss, 1987 [38]	Observational clinical study	300 RA patients contacted. 6 underwent food challenge tests.	Self-reported exposure to foods suspected. Clinical evaluation and allergy testing. Elimination of food (pork)	No immunologic reaction detected during controlled food challenges	Self-reported symptoms; limited food and number of patients. Fair quality.
Van de Laar et al., Netherlands, 1992 [39]	Double-blind randomized controlled clinical trial	94 RA sieropositive patients. Disease activity was substantiated by the presence of at least three of the four following criteria: (a) erythrocyte sedimentation rate > 28 mm/h; (b) morning stiffness >45 min; (c) more than five tender joints; and (d) more than two swollen joints.	Blinded food challenge. 2 diets; 1 was free from all potentially allergenic components, additives, and preservatives; 2 contained milk allergens and azo colorings, and was free from other potentially allergenic materials, additives, and preservatives. Evaluation at baseline, after 4 weeks of diet, after reintroduction of normal diet.	Modest subjective improvements during diet (morning stiffness, tender/swollen joints, fatigue, global assessment). No significant difference between allergen-free vs. allergen-restricted diets and objective markers (ESR, CRP, RF) showed no significant change.	Short duration, limited to seropositive RA. Good quality
Van de Laar et al., Netherlands, 1992 [40]	Double-blind clinical trial	6 patients RA sieropositive patients, who have shown improvement on a hypoallergenic artificial diet in the precedent study	Clinical assessment and intestinal biopsies during elimination diet	4 patients had partial or total remission during allergen free feeding. In 2 patients, a marked reduction in mast cells was noted in synovial membrane and proximal small intestine during allergen elimination.	Very small sample; highly selected patient population. Good quality.
Kavanagh et al., UK, 1995 [41]	Double blind randomized controlled clinical trial	47 RA patients	A diet without chicken, fish, rice, carrots, runner beans and bananas was taken for 4 weeks and was followed by a period of food reintroduction.	The diet group lost more weight than the control group and this correlated with the improvement in grip strength.	Limited effects control. Good quality.
Holst-Jensen et al., Denmark, 1998 [42]	Randomized controlled trial	30 patients with active RA	Peptide diet elemental diet in intervention group and usual diet in control group. 4 weeks of diet.	Temporary clinical improvement in the diet group (average pain level, functional disability)	Small simple size, inconsistent changes in markers. Good quality.
Hafström et al., Finland, 2001 [43]	Randomized controlled trial	66 RA patients	The patients were randomized to receive either a vegan diet, free of gluten or a non-vegan diet for 1 yr.	IgG antibody levels against gliadin and b-lactoglobulin dropped in the vegan diet-treated patient’s group. There was no delay in the radiological annihilation of evidence in each of the groups.	Modest control of bias. Fair quality

.

The articles included were written between 1986 [36] and 2001 [37,43]. They were set in the following countries: USA [36], Italy [37], Switzerland [38], Netherlands [39,40], the United Kingdom [41], Denmark [42] and Finland [43]. The design of the studies included two observational studies [38,40], one case report [39] and five randomized controlled trials [39,40,41,42,43]. All the participants in the studies were patients with rheumatoid arthritis treated with a specific diet or the elimination of antigens [37,38,39,40,41,42,43].

The association between diet, food hypersensitivity, and rheumatoid arthritis appears to be varied and restricted to a subset of individuals in the currently available clinical research. According to the studies by Panush et al. [36] and Pacor et al. [37], certain foods, especially milk and wheat, may trigger flare-ups of inflammatory arthritis in some individuals. Symptoms may resolve during fasting or elimination diets, but they may return when food is reintroduced. Both IgE-mediated and non-IgE-mediated immunological pathways are suggested in these studies. The variability of self-reported food-related symptoms was highlighted in the larger observational studies failing to demonstrate immunological reactions during controlled meal challenges [38] with little to no impact on objective inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Randomized controlled trials assessing elimination or elemental diets [39,40,41,42,43] showed modest and mostly temporary improvements in subjective clinical outcomes like pain, morning stiffness, grip strength, and functional disability

Table 2. Mapping of the Mechanism of each study included.

Author, Country, Year	Design/Number of Participants	Intervention	Results	Proposed Mechanism
Panush et al., USA, 1986 [36]	Prospective blind case (n = 1)	Fasting for 3 days	Flare reproduced; subjective improvement on the elimination of the antigens	Non-IgE immunological complex
Pacor et al., Italy, 2001 [37]	Case reports (n = 2)	Elimination + DBPC challenge	Flares on milk/wheat; resolved on diet	IgE + mixed
Felder et al., Swiss, 1987 [38]	Observational (n = 300)	Self-reported avoidance	Variable symptoms; no objective change	Unspecified
Van de Laar et al., Netherlands, 1992 [39]	Double Blind-RCT (n = 94)	Allergen-free vs. restricted	Modest subjective gain; no ESR change	Barrier/microbiome
Van de Laar et al., Netherlands, 1992 [40]	Double Blind-RCT (n = 6)	Elimination + intestinal biopsy	↓ mast cells; partial remission	Cell-mediated
Kavanagh et al., UK, 1995 [41]	Double Blind-RCT (n = 47)	Hypoallergenic diet 4 weeks	Improved grip strength; ESR stable	Barrier/microbiome
Holst-Jensen et al., Denmark, 1998 [42]	RCT (n = 30)	Peptide elemental diet	Temporary pain reduction	Innate cytokine modulation
Hafström et al., Finland, 2001 [43]	RCT (n = 66)	Vegan gluten-free diet 1 yr	Drop of IgG to gliadin; no radiographic change	Adaptive IgG tolerance

summarises all the mechanism of each of the included studies.

Significantly, a carefully chosen subset of patients who reacted to hypoallergenic diets displayed immuno-histological alterations, including decreased mast cell numbers in intestinal and synovial tissues, as well as partial or total remission. Long-term dietary therapies, such as gluten-free and vegan diets [44], were associated with lower levels of food-specific IgG antibodies but had no discernible effect on the course of radiographic illness. Overall, our results suggest that while no consistent or long-lasting therapeutic effect has been shown in unselected populations, dietary therapies may offer symptomatic relief in a small, carefully chosen cohort of RA patients.

The quality of the studies was rated as “fair” in four studies [36,37,38,43] and “good” in four articles [39,40,41,42].

4. Discussion and Limitations

Despite decades of research, the significance of food hypersensitivity and dietary therapies in rheumatoid arthritis is still unclear and has little proof. Case reports, small observational studies, and a few randomized controlled trials conducted primarily between the 1980s and late 1990s make up the scant literature that is currently available [37,38,39,40,41,42,43]. Others in the literature, such as Gamlin et al. [45], consistently concluded that no discernible or repeatable benefits can be shown at a population level and that dietary modification may only result in symptomatic improvement in a small percentage of patients. According to previous evaluations [39,40,44,45,46], the benefits observed are highly personalized and unpredictable, and that food intolerance does not reflect a general pathogenic mechanism in RA.

While objective inflammatory markers such as ESR and CRP typically showed little to no change, improvements relating to elimination or elemental diets were primarily subjective, and involved pain, morning stiffness, fatigue, or functional impairment throughout controlled trials. Gamlin [45], in his study, also pointed out that methodological flaws, such as insufficient blinding, inconsistent dietary protocols, and challenges in identifying triggering foods, significantly undermine causal interpretation, despite the fact that approximately one-third of patients in some studies seemed to improve during elimination diets. Furthermore, these benefits were frequently fleeting and vanished when a regular diet was resumed.

From a molecular perspective, hypothesized links between food exposure and RA, such as immunological cross-reactivity with microbial antigens, IgE-mediated allergy, non-IgE-mediated hypersensitivity, and increased intestinal permeability, remain hypothetical and inconsistently supported. Gamlin [44] also pointed out that even studies that reported immuno-histological alterations, including decreased mast cell density after elimination diets, were restricted to extremely small, carefully selected patient groups [39,40]. Importantly, almost all of the studies that are currently accessible were conducted before modern RA therapy techniques, such as early aggressive treatment, biologic and targeted synthetic DMARDs (Disease-Modifying Antirheumatic Drugs), and standardized composite disease activity indexes. As a result, their applicability to current clinical practice is significantly limited.

In conclusion, the convergence of primary research and narrative reviews [43], suggests that although food hypersensitivity may influence symptoms in certain people, the evidence base is inadequate, out-of-date, and methodologically flawed. Dietary therapies should, at most, be taken into consideration on an individual basis and cannot be advised as a general therapeutic approach in RA. To ascertain if food hypersensitivity is a causative, contributing, or merely epiphenomenal factor in disease activity, well-designed, sufficiently powered investigations in contemporary RA cohorts are needed.

5. Conclusions

A conclusive or widespread role for dietary modifications or food sensitivities in the treatment of rheumatoid arthritis is not currently supported by the available data. While elimination diets or regulated dietary alterations may provide some people with subjective symptom relief, these reactions seem inconsistent, and are not supported by consistent improvements in objective disease measurements.

Dietary therapy cannot be recommended as the standard treatment for rheumatoid arthritis due to the methodological limitations of current studies and the lack of strong, repeatable therapeutic benefits across larger patient populations. Rather, such methods should only be taken into consideration on an individual basis, with close observation and reasonable expectations.

To ascertain whether food-related immune pathways have a significant impact on disease activity, future studies involving modern patient cohorts, standardized dietary regimes, and stringent clinical outcomes are necessary. Until such data are available, dietary therapies should be considered exploratory, rather than proven therapeutic techniques in the treatment of rheumatoid arthritis.

Moving forward we suggest that large, randomized trials should be designed in order to explore different therapeutic techniques integrating dietary interventions with current pharmacologic regimens. A future clinical trial proposal could include different treatment arms such as:

• DMARDs only;
• DMARDs + specific diet (for example: gluten-free, vegan, or Mediterranean);
• DMARDs + exercise;
• DMARDs + diet + exercise;
• Diet + exercise without DMARDs.

The outcomes measured should include patient-reported outcomes, CRP/ESR, microbiome shifts, and IgE/IgG food-specific antibody profiles and quality-of-life indices. Also controlled nutrition and immunogenetic stratification could reveal which arthritis subtypes show genuine diet responsiveness. Such a trial could clarify whether the diet can influence outcomes as an adjunct modulatory factor or rather can be used as a primary therapy.