>>CLINICAL FOCUS What About Diet? The Complex Relationship between Food and Atopic Dermatitis Exploring the clinical implications of our current understanding of diet and eczema. BY SARA N. BILIMORIA AND PETER A. LIO, MD In the past decade, prodigious the causation and treatment of the lat- unreasonable notion, as about one >> leaps in the understanding of ter...”4 In a more contemporary take, third of moderate to severe AD atopic dermatitis (AD) have begun the National Institute of Allergy and patients have verifiable food allergies: to flesh out the picture of a complex Infectious Diseases (NIAID) stated that type I hypersensitivity reactions with and multifactorial disease.1 While skin it, “does not mean to imply that atopic hives, angioedema, or anaphylaxis.11 barrier dysfunction may well be the dermatitis results from food allergy,” Such a reaction constitutes bona fide primary or “root cause” in some or and that “... the role of food allergy in food allergy and remains a critically perhaps even most patients,2 it has also the pathogenesis and severity of this important consideration for patients. been conclusively demonstrated that condition remains controversial.”5 Although correlation most certainly barrier damage can occur as a second- It continues to be a contentious does not equal causation, it can be ary phenomenon in the presence of area, with many families and health hard to ignore the power of their inflammation.3 This underscores the care practitioners promoting the allergenicity: a single bite is often fact that barrier impairment is always idea that food is an important driver enough to trigger an impressive an important aspect of AD, regardless of eczema.6 In a recent study of 211 immediate reaction. While this of its primacy. Thus, the stage is set for patients with AD, more than half reaction could secondarily trigger an a deeper exploration of the complex (57 percent) reported discussing AD flare, it is fundamentally different relationship between AD and diet. In diet with a health care provider, but from a primary eczematous response, this brief review we will explore some over one third (38 percent) felt the and assuredly not what people are of the key studies that have shaped the discussion was unhelpful.7 In the same talking about when searching for thinking about this contentious rela- report, 68 percent of children were causative foods. tionship, culminating in a very current reported to have excluded foods Several studies have sought to sepa- viewpoint that suggests that the skin from the diet. Another study found rate these concepts of food allergy and barrier dysfunction of AD may actually that the perceived prevalence of food what might be called ‘‘food-induced drive the development of food allergy, intolerance is more than 10 times atopic dermatitis.” In a carefully con- and not the other way around. higher than the true prevalence,8 and trolled environment, 19 children with others confirm the fairly widespread severe, unremitting atopic dermati- CONNECTIONS practice of untested and unsupervised tis were challenged with test foods Diet has long been implicated in the dietary modification in an attempt and observed for a worsening of AD pathogenesis of AD, and this relation- to control AD, with up to 71 percent rather than an urticarial response. ship has been fraught. A paper in the of patients having made a dietary Remarkably, only one patient had British Medical Journal from 1830 sum- change.9,10 It is abundantly clear that worsening AD after food challenge.12 marized it by saying: “There is probably there are clinical gaps in this area that Another study by Hill, et al. sought no subject in which more deeply rooted require addressing. delayed eczematous reactions several convictions have been held…as regards Food driving AD is not an days after a cow’s milk challenge, and 76 PRACTICAL DERMATOLOGY DECEMBER 2019 CLINICAL FOCUS << ©istockphoto Optimizing topical care takes on “ new importance, as an impaired barrier may be a gateway to transcutaneous sensitization and actually developing allergies if left unchecked. At the same time, it is difficult to argue against recommending a healthy diet, as there is little doubt that eating well promotes health in every organ system, including the skin.” found evidence of such in only 28 out at play—regardless of the mechanism is more severe and undertreated, of 135 children, or about 20 percent or any test results, the patients simply certain factors may be more likely to of these highly-selected patients with seemed to be able to tolerate foods trigger a flare than when things are a history strongly suggestive of cow’s that they previously had suspected as better controlled. This is particularly milk allergy.13 Importantly, 12 of the being triggers. relevant when invoking non-allergic 28 positive cases (43 percent) had This draws two possibilities into the mechanisms for potential food-related negative skin prick tests to cow’s milk light: the first is the idea that much exacerbations. This area remains allergen, suggesting an alternative of the concern about foods is emo- somewhat murky, but is important to pathogenesis than type I allergy. Finally, tional and/or psychological. There is consider, as some foods may simply all of the patients with eczematous significant literature that highlights be pro-inflammatory, working to exacerbations, save one, showed associ- the power of placebo in dietary exacerbate the disease outside of a ated gastrointestinal and/or respiratory change across several disease states, specific allergic mechanism.20,21 manifestations, making an isolated and it would not be surprising if this While these studies certainly do not eczema flare an extremely rare occur- at least partially explained some of disprove true food-induced AD, and rence. these cases.15–18 This is magnified in in fact validate its existence to some A striking study by Thompson and the context of a waxing and waning degree, they underscore how rare it Hanifin demonstrated another poten- disease like AD, in which it has been is, even in carefully selected high-risk tial facet of this relationship. They convincingly argued that misattribu- patients. Moreover, they confirm that found that in 80 percent of cases in tion is common and presumably works such an eczematous reaction does not which patients were convinced that in both directions: that food can cause correlate with skin prick or serologic food was a significant factor contribut- AD as well as that excluding foods can testing in a reliable way, calling their ing to their AD, such concerns became improve it.19 use into question for this specific negligible once better control of the The second possibility, admittedly clinical scenario. The Hill, et al. study eczema was achieved.14 Importantly, very speculative, is that there may underscores the rarity of an isolated such a finding helps to dismiss the idea be something of a threshold effect eczematous response, with nearly that non-allergic mechanisms could be at play. That is to say, when eczema all of the patients having associated DECEMBER 2019 PRACTICAL DERMATOLOGY 77 >>CLINICAL FOCUS gastrointestinal or respiratory symptoms as well. Finally, more closely to gain insight into the subtleties therein. the Thompson and Hanifin study raises the specter of non- In 1978, Atherton, et al. performed a 12-week double- specific inflammatory effects playing a small role, possibly blind, controlled, crossover trial of an egg and cow’s milk modulated by background disease severity. exclusion diet in 36 children with AD. They found that 14 This may be a good point to outline at least provisional patients responded better to the exclusion diet than to definitions for some of the terminology discussed: the control diet, whereas only one responded better to the • Sensitization or Sensitivity can be defined as having control diet.23 Notably, there was no correlation between a positive IgE blood testing or skin prick testing to a food positive skin prick test and response to the exclusion diet, regardless of clinical applicability. suggesting that this was not type-I allergy mediated. • IgE-mediated food allergy refers to a clinical response to Businco, et al. placed 59 children on a four-week elimina- a food, including urticaria, angioedema, or anaphylaxis tion diet of cow’s milk, eggs, or both (depending on their in someone who is sensitized. diet), and reported an almost unbelievable 80 percent clini- • Food intolerance is a broader category including non- cal improvement.24 Critically, the mean age of those who immunologic issues such as inability to digest lactose responded was significantly younger than those who did not (“lactose intolerance”), but may also include irritable respond (3.5 vs 4.7 yrs) (p < 0.01). The authors attempted bowel syndrome, reactions to sulfites, and even the to justify this by positing that the foods were more likely to immune-mediated disease celiac sprue in some taxono- be part of the younger children’s diet. Here again, they con- mies. cluded that skin prick tests and serum IgE tests would not • Less-specific “inflammatory” foods and “anti-inflam- be helpful for predicting benefit. matory” foods that may indirectly contribute to or Other studies have been less convincing. What do we modulate against some degree of inflammation in the make of the double-blind randomized controlled trial of body either directly or indirectly through better overall egg and cow’s milk exclusion diet completed in 40 patients health, weight loss, and even through the powerful pla- over six weeks by Neild, et al.?25 They found no statistically cebo effect of feeling better about one’s health and diet. significant differences in skin area affected, itching, or topi- cal steroid use between the groups. And what about the IS THE PROOF IN ELIMINATING THE PUDDING? study of 29 children with AD on a two-week elimination We have thus far looked at scenarios that utilize food diet? It showed significant improvement in itch and body challenge, but do exclusionary diets improve AD? While surface area affected by eczema, challenging the conclusions the notion of simply removing troublesome foods remains of the Neild, et al.