John J. Zone, MD
Dr Zone has treated over one thousand patients with Dermatitis Herpetiformis (DH). It usually presents as itchy, red bumps in the elbows and knees. DH should be diagnosed through a biopsy and Dr Zone recommends biopsying in the area close to redness, but not directly on the red bumps.
There have been several studies looking at the prevalence of DH. The numbers in Europe are very similar to those of the United States. It is a genetic disease but it is distributed throughout life. We don’t know what the factors are that set off the onset of disease. We do, however, know that people with DH express the entire range of intestinal abnormalities. Some people will have Grade IV and others will only have Grade I.
Dr Zone stresses another important point that people with DH develop antibodies to epidermal transglutaminase (TG3). Dr Zone states that roughly one in six celiac patients will develop DH.
What about people who have intestinal inflammation, but don’t have DH or symptomatic CD?
It is important to consider that celiacs may have:
- Only aphthous stomatitis
- Only eczema
- Only alopecia areata
- Only psoriasis
- Only fatigue or anemia
What this means is that all of the diseases mentioned above might be associated with celiac disease, it is pretty rare, but those people who have it might get better on a gluten free diet.
A 1998 paper studied oral ulcers and celiac disease. They found that approximately five percent of patients with “idiopathic” apthous stomatitis have been found to have positive endomysial antibody tests and then CD on small bowel biopsy. Stomatitis will clear with a gluten free diet. (Jokinen J et al: Celiac sprue in patients with chronic oral mucosal symptoms. J Clin Gastroenterol.1998; 26:23-26) In a 2008 study, the researchers looked at 269 kids ages 3 to 17 with CD and 575 otherwise healthy subjects. They found apthae in 61 of the 269 kids (22.7%) and 41 of the 575 normals (6%). 33 out of 46 CD kids on a strict gluten-free diet reported significant improvement or clearing of apthae. (Campisi et al. Dig Liver Disease. 2008 40:104-107)
Alopecia Areata (AA)
Alopecia areata is a T-cell mediated disorder that produces hair loss. Some studies have shown that patients with AA and CD have regrown hair with a gluten free diet (GFD) others have seen no effect of GFD. Also of note, chronic diseases can make the response to a GFD less likely. Dr Zone states that there is probably about one in 100 chance of having celiac disease. The questionable association between CD and AA and hair regrowth will only be answered by a prospective trial of testing new onset AA kids for total serum igA and tTG, establishing CD rate, and then comparing the outcome on GFP compared to non CD kids on a normal diet.
CD and Psoriasis
Take Home Point—CD occurs at a slightly increased frequency in psoriasis patients and response to a GFD has been reported.
A 2002 study of patients with long standing psoriasis who were found to have CD all had marked improvement on a GFD. Psoriasis patients with positive anti-gliadin antibodies have improved on a GFD. The prevalence of positive EMA and tTG antibodies is no greater than the rest of the population (1:133). The question is “is gluten a source of chronic antigen stimulation in psoriasis?” (Cardinali et al. Br J Derm. 2002.147:187-188)
CD and Atopic Dermatitis
There is no increased incidence of atopy in CD patients but patients with dermatitis who are shown to have CD will improve on a GFD. This was a large case controlled study of 82 CD patients and 180 matched controls and their first-degree relatives. The researchers found increased prevalence of asthma, eczema, rhinitis, or elevated IgE levels. However, patients with eczema and Cd did improve their eczema on a GFD. (Greco L, et al. Paediatr Scand. 1990 79:670-74)
Take Home Points
- Screening in patients with these disorders (serum IgA and IgA tTG(TG2)) will result in 1-2% positivity (low yield)
- But: Patients with a (+) result who are then treated with a Gluten Free Diet will likely likely have response of their skin disorder to dietary restriction of gluten
What about people who are “gluten sensitive?”
There is a group of people who have gone on gluten free diets and say that they feel better. These are people with normal IgA tTG and normal small bowel biopsies. Up to 50 percent of these people do have the high-risk genotype (higher than the 25 percent in normals). A 2012 studied demonstrated that certain symptoms can improve with dietary gluten restriction including GI symptoms, neurological symptoms, skin symptoms and “brain fog” (the most common symptom). These were all patients with a normal intestinal biopsy. (Lundin EA and Alaedini A:Non-gluten sensitivity. Gastrointest Endosopy Clin N Am. 2012. 22: 723-734) A study at the University of Maryland documented that symptoms could be induced by gluten through a blinded challenge that they performed at the university.
In patients with non-celiac gluten sensitivity, adaptive immune response (IgA, tTG, IgE anti wheat and cellular response to gliadin, etc.) cannot be identified. These patients have normal intestinal biopsies and multiple symptoms in response to gluten ingestion that do not occur with placebo. These people may have an innate immune response that can occur in the absence of HLA DQ2. There are also no serologic markers.
This is the most common question that Dr Zone hears from colleagues. Dapsone is a major oxidant stress to red blood cells. It is important to make patients aware of hemolytic anemia and the blue/gray color associated with methemoglobinemia. Clinical management should stress the maintenance of the smallest dose necessary to control the disease. Occasional new DH lesions (2-3/week) are to be expected, and are not an indication for raising the dose. Before initiating Dapsone treatment, you should perform a baseline CBC and Chem profile; G-6-PD in asians, blacks or those of southern mediteranean descent. You should start your patients at 25 mg. daily and increase 25 mg. weekly until the symptoms are controlled. CBC should be performed weekly for four weeks, then monthly for six months, then semi-annually. Chem profile should be performed at six months and then annually.