Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Karen Pendergrass
What was studied?
This study examined the prevalence of nickel (Ni) allergic contact mucositis (ACM) in celiac disease (CD) patients who were in serological and histological remission from their condition but continued to experience relapsing gastrointestinal and extraintestinal symptoms despite following a strict gluten-free diet (GFD). Additionally, the study investigated the therapeutic effects of a low-nickel diet on these persistent symptoms in the CD patients. The study hypothesized that Ni-rich foods, which are commonly consumed in a GFD, might lead to intestinal sensitization to Ni and induce symptoms similar to irritable bowel syndrome (IBS).
Who was studied?
The study recruited 102 consecutive CD patients (74 female, 28 male, age range 18–65 years) who had been on a GFD for at least 12 months and were in serological and histological remission (Marsh–Oberhuber type 0–I). These patients continued to report relapsing gastrointestinal and/or extraintestinal symptoms despite adherence to the GFD. After applying exclusion criteria (e.g., lactose intolerance, Helicobacter pylori infection, inflammatory bowel diseases), 20 female patients completed the study. All these patients underwent nickel oral mucosa patch testing (omPT) and were subsequently placed on a low-nickel diet for three months.
What were the most important findings?
Prevalence of Ni ACM in CD patients: The study found that 100% of the CD patients who completed the study tested positive for Ni ACM using the omPT, suggesting a high prevalence of nickel sensitivity in CD patients experiencing recurrent symptoms despite a GFD.
Symptom trends and the impact of a low-nickel diet:
Following an initial gluten-free diet (T0 vs. T1), 79.2% of the total symptoms improved, with 58.3% showing statistically significant improvement. However, after prolonged adherence to a GFD (T1 vs. T2), 83.3% of symptoms worsened, with 41.7% of symptoms showing statistically significant exacerbation. This relapse of symptoms was attributed to increased dietary intake of Ni-rich foods commonly consumed in a GFD (e.g., corn). After three months of a low-nickel diet (T2 vs. T3), 83.4% of symptoms improved, with 41.7% showing statistically significant improvement. Both gastrointestinal and extraintestinal symptoms showed substantial relief, including key symptoms such as abdominal pain, bloating, fatigue, and dermatitis.
What are the greatest implications of this study?
Nickel sensitivity as a cause of persistent symptoms in celiac patients: This study suggests that nickel sensitivity (Ni ACM) may be a significant underlying cause of persistent gastrointestinal and extraintestinal symptoms in CD patients who are in remission but continue to suffer despite adherence to a GFD. The findings imply that the ingestion of Ni-rich foods commonly included in a GFD might trigger or exacerbate these symptoms in Ni-sensitive individuals.
Clinical management of celiac disease: The results highlight the potential clinical importance of considering nickel sensitivity in CD patients with unresolved symptoms. Nickel oral mucosa patch testing (omPT) should be considered as part of the diagnostic workup for such patients, and a low-nickel diet (LNiD) could be an effective therapeutic intervention to alleviate these symptoms. This could lead to an improved quality of life for CD patients and more targeted dietary interventions.
Potential changes in dietary guidelines: If larger studies confirm these findings, dietary guidelines for celiac patients may need to be expanded to include advice on limiting Ni-rich foods, particularly for patients who are unresponsive to a GFD alone. This could represent a significant shift in how refractory or non-responsive celiac disease is treated.
Overlap with other dietary interventions: The study also draws attention to the overlap between nickel-rich foods and foods commonly eliminated in low-FODMAP diets, which are often prescribed for IBS-like symptoms. This suggests that some benefits attributed to low-FODMAP diets may, in fact, be due to the concurrent reduction of nickel intake, further emphasizing the need for specific diagnostic testing in dietary management.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.