New NEA Research: What Factors Influence Clinical Trial Participation for…
The findings highlight the differences between what adults value for themselves in clinical trial participation versus what parents find important for their children.
Published On: Feb 3, 2016
Last Updated On: Jul 15, 2021
As a first year medical student, I recall a wonderful lecture on being a “medical detective,” on using all the clues — and a great deal of persistence — to solve a diagnostic puzzle. One of the cases described in that lecture was that of a healthy young woman who was becoming increasingly ill without a clear diagnosis. She had diarrhea, weight loss, fatigue, and an itchy rash on her elbows and knees. She saw doctor after doctor, but eluded a diagnosis. Some even thought she was crazy. Finally, it was a dermatologist who solved the case: it was dermatitis herpetiformis, the rash associated with gluten sensitivity and her underlying celiac sprue! At the time, this diagnosis was portrayed as rare and obscure, as was the then-seemingly-impossible treatment: a gluten-free diet.
It is thus remarkable now to see sections of supermarkets and, indeed, entire restaurants, boasting that they are “gluten-free,” and it seems that the most frequent dietary recommendation from holistic practitioners to our eczema patients has been “avoid gluten.” This once obscure disease has become mainstream and is at the forefront of our collective consciousness. But is there merit to this? Do the 25,000+ happy years of humans eating gluten belie a darker truth? And, most importantly for us, is it possible that going gluten-free could improve or even cure eczema?
Evidence exists that gluten has been a staple of the human diet since the dawn of the Stone Age and, despite the fact that gluten intolerance has been known in the medical community for quite some time, only in recent times has gluten garnered such lavish time in the spotlight. While some have turned to a gluten-free diet in response to a true gluten sensitivity, many others have turned to the lifestyle for its purported anti-inflammatory effects, decrease in diet-associated bloating, weight loss, and general effects on well-being. In the medical literature, there are studies that examine the relationship between gluten and everything from autism to ulcerative colitis, diabetes, arthritis, and neurological disorders (ElChammas, 2011). In response, grocery stores now dedicate entire sections to gluten-free products, trendy new restaurants promote a gluten-free lifestyle, and people have started to consider gluten in the diet as the source of many of their ills. It is no surprise that given this increased popularity, even those without gluten intolerance are turning to this diet in hopes of achieving a healthier way of life.
Gluten has received its fair share of negative press and has been implicated in a number of dermatologic disorders. Dermatitis herpetiformis (DH), as it relates to celiac disease, remains the archetype of gluten-associated skin disorders. Indeed, by its very definition, the removal of gluten products from the diet results in clearance of the skin. While some patients may present with the classic itchy bumps and small blisters on a normal or reddish base, each patient may vary in terms of overall presentation. There is no doubt that DH can look very similar to atopic dermatitis in some patients, and we have had several DH patients over the years who have been misdiagnosed with eczema.
In order to understand a bit more about gluten and DH, however, we must discuss celiac disease. Approximately 4 out of every 5 patients with DH have celiac disease, a relatively common condition affecting up to 1 out of every 130 people in the United States.
Celiac disease is an immunologically-mediated disease in which a patient has an autoimmune reaction against the intestines. These patients are diagnosed in part through blood testing: antibodies against gliadin, a part of gluten, are commonly detected in patients with celiac disease. The most sensitive and most specific antibodies particular to celiac disease, however, are the endomysial antibodies that are present in 4 out of every 5 patients with DH and in virtually all patients with active celiac disease (Adams, 2011). Remarkably, endomysial antibodies often become undetectable after several months of a gluten-free diet, suggesting deeper improvement than just symptomatic relief in the skin. Despite this, some 6 to 9 percent of patients with celiac disease have normal antibodies. Surprisingly, these “normal” patients generally have a more severe disease manifestation, for reasons that are not clear (Klapproth, 2011). Therefore, it is possible to miss this diagnosis on blood testing alone.
DH has been associated with other autoimmune diseases, and researchers have begun to explore the relationship between DH and many immunologic diseases like eczema, psoriasis, and alopecia areata. While many of these associations are based on anecdotal evidence of individuals who improve once gluten is removed from the diet, several small studies suggest that the association between the aforementioned skin diseases and gluten may be real—at least in some patients. Other studies seem more dismissive of this possibility.
One very provocative study found that 30 percent of adults with atopic dermatitis had detectable antibodies to gliadin in contrast to only 6.5 percent in the general population (Finn, 1985). It is important to note, however, that this was a relatively small study of only 56 patients, and that simply having the antibodies does not necessarily mean that this was the cause of the eczema. Still, the result suggests that perhaps for some patients, certain environmental and dietary factors could create an immune response that could be fueling other inflammatory conditions in the body.
A more sobering study evaluated 90 children with proven celiac disease and a personal or family history of allergies and atopic dermatitis. When compared to a control group without celiac disease, there was no difference found in the number of patients with allergies or atopic dermatitis between the groups (Cataldo, 2001). If gluten sensitivity was really associated with atopic dermatitis, we would have expected to see a much higher rate in patients with known celiac disease, and this simply was not the case. Yet a study in 2004 examined over 1,000 adults with celiac disease and found that atopic dermatitis was about three times more common in patients with celiac disease than in the general population (Ciacci, 2004). It is fascinating to point out, however, that one year on a gluten-free diet did not change the amount of atopic dermatitis and allergies found in the celiac patients in this study.
Finally, to demonstrate just how slippery this question is, investigators from Italy studied patients with allergies and found that nearly 30 percent had changes in the bowel that were suggestive of gluten sensitivity — but all had negative blood tests for celiac disease. In this study, when the patients were placed on a gluten-free diet for six months and retested, the severity of their allergy and bowel symptoms were significantly improved (Massari 2011). Critically, all of the patients in this study had both allergies and bowel symptoms such as diarrhea, stomach pain, and weight loss. This is a very important caveat and represents a highly-specific subgroup of allergy patients. Sadly, that is the end of the trail. We await larger and better-designed studies to look at the effect of a gluten-free diet in patients with atopic dermatitis before we can make a final judgment. But what to do in the meantime?
Because the idea is scientifically plausible, and because gluten-free foods have become much more available than they were even five years ago, a trial of a gluten-free diet may be an option for certain patients, with some caveats.
First of all, this is not for everyone. Generally speaking, the patients for whom this could be considered have severe, refractory eczema. They will have already seen an allergist and had testing for both food and environmental triggers. Ideally, they will also have had patch testing for contact allergies, which can fuel eczema both when touching the skin but also when eaten (such as nickel and balsam of Peru). Given the studies we’ve discussed above, testing for celiac disease seems irrelevant, but if there are any bowel symptoms, seeing a gastroenterologist for further evaluation is a must.
Above all else, this is not a diet for the very young. Going gluten-free brings the potential for a very unhealthy diet. Without careful balance and monitoring, the diet may lead to a deficit in fiber, vitamin D, magnesium, and selenium, while also leading to relatively higher intakes of sugars and saturated fats (Ohlund, 2010). Additionally, despite some individuals trying a gluten-free diet for weight loss, a study in 1998 demonstrated that patients on the gluten-free diet had a higher rate of obesity than patients with celiac disease who were not gluten free and people in the control group without celiac disease (Mariana, 1998). There are also cost considerations. A recent paper demonstrated that gluten-free foods cost up to 500 percent more (Singh, 2011).
Despite these challenges, and despite the fact that we have seen many patients who have tried the diet in earnest and have not seen improvement, for those with severe, refractory eczema a trial of a gluten-free diet could be worthwhile. Ideally, a dietitian would be consulted at the start of the trial, and careful adherence to the diet would be maintained during the gluten-free period. Although there seems to be no consensus, four to eight weeks should be sufficient for most to show signs of improvement in the skin. Indeed, in DH the improvement is usually measured in days.
As we learn more about the immune system and atopic dermatitis, there is no doubt that many mysteries will be revealed. There are clear signs that what we eat can affect our skin, although for those with atopic dermatitis, there seem to be no easy answers. In the meantime, we venture forth, searching in the darkness, waiting to see the light.
Adams S. “Interpretation of celiac disease blood test results,” Celiac.com, http://www.celiac.com/articles/57/1/Interpretation-of-Celiac-DiseaseBlood-Test-Results/Page1.html (accessed May 26, 2011).
Klapproth J. “Celiac sprue,” eMedicine.medscape.com, http://emedicine.medscape.com/article/171805-overview (accessed May 26, 2011).
Finn R, Harvey M, et al. “Serum IgG antibodies to gliadin and other dietary antigens in adults with atopic eczema,” Clinical and Experimental Dermatology, April 1985; 10(3): 222–228.
Cataldo V, Marino P, et al. “Celiac Disease and Risk of Atopy in Childhood,” Pediatric Asthma, Allergy & Immunology, June 2001; 15(2): 77–80.
Ciacci C, Cavallaro R, Iovino P, et al. “Allergy Prevalence in Adult Celiac Disease,” Journal of Allergy and Clinical Immunology, June 2004; 113(6): 1199–203.
El-Chammas K, Danner E. “Gluten-free diet in nonceliac disease,” Nutrition in Clinical Practice, June 2011; 26(3): 294–9.
Massari S, Liso M, De Santis L, et al. “Occurrence of Nonceliac Gluten Sensitivity in Patients with Allergic Disease,” International Archives of Allergy and Immunology, February 22, 2011; 155(4): 389–394.
Ohlund K, Olsson C, et al. “Dietary shortcomings in children on a gluten-free diet,” Journal of Human Nutrition and Dietetics, March 23, 2010; 23(3): 294–300.
Mariana P, Viti MG, et al. “The gluten-free diet: A nutritional risk factor for adolescents with celiac disease?” Journal of Pediatric Gastroenterology and Nutrition, November 1998; 27(5): 519–523.
Singh J, Whelan K. “Limited availability and higher cost of gluten-free foods,” Journal of Human Nutrition and Dietetics, May 24, 2011. doi: 10.1111/j.1365- 277X.2011.01160.x.