rosacea blog

I couldn’t find any scientific publication on the topic of gluten sensitivity and rosacea, but if you do a search online, then you’ll find plenty of information on the topic (mostly in forums and message boards).

As it turns out, many people with rosacea wonder if their rosacea symptoms are caused by a gluten sensitivity. Some have been successful in reducing their rosacea symptoms by following a gluten-free diet. As I and others have written before, there seems to be a digestive component to rosacea.

Gluten is a protein that’s abundant in certain grains, mostly wheat, barley and rye. The gluten itself is a protein made up of two protein parts, gliadin and glutenin. The gliadin part is responsible for the abnormal immune reaction that causes gluten sensitivity and celiac disease. Between 0.5 and 1% of the world’s population suffers from gluten-sensitivity. Gluten sensitivity is not the same as a gluten allergy. The gluten proteins of corn and rice lack the gliadin part and do therefore not cause any sensitivity.

The immune system’s overreaction to wheat’s gluten causes celiac disease, in which the lining of the small intestine becomes chronically inflamed. Symptoms of celiac disease include chronic diarrhea, cramps, bloating, fatigue and malabsorption of essential nutrients, which could result in secondary symptoms such as psychological and neurological problems.

The gluten sensitivity makes it difficult for the body to absorb vitamins, in particular vitamin D. This could explain the possible involvement of vitamin D in rosacea and autism that I described recently. Many children with autism have seen their symptoms improve after staring a gluten-free diet.

Whether a potential gluten sensitivity is involved in the development of rosacea symptoms, it is possible that the inflammation of the intestines contributes to an overall stronger inflammatory response in the facial skin of rosacea patients. While there are many rosacea trigger factors, pizza (loaded with gluten and histamine) is one food that probably should be limited in your diet if you have rosacea.

Additional Reading

• The Storm Before The Calm: Why Some People Get Temporarily Worse … – by Elaine Fawcett, MJ, NTP. It seems like a dirty trick. You’ve learned you’re gluten intolerant and are hoping a gluten-free diet will cure your eczema, diarrhea, or whatever niggling health malady vexes you. …

Rosacea is associated with many different trigger factors. Recently, another potential trigger factor for rosacea was described. It appeared that men who had been taking drugs for erectile dysfunction, were developing rosacea symptoms.

The erectile dysfunction (ED) drugs these men were taking belong to a class of drugs called Phosphodiesterase 5 Inhibitors (PDE5i). Phosphodiesterase 5 inhibitors are not just used to treat ED, but also conditions such as pulmonary hypertension and Raynaud’s phenomenon.

Phosphodiesterase enzymes play an important role in regulating certain signaling pathways inside the cell. The PDE5 enzymes are associated with regulating the Nitric Oxide (NO) signaling pathway. NO, generated from the amino acid L-Arginine, is released from nerves and endothelium and causes smooth muscle cells lining the blood vessels to relax, which increases blood flow. Inhibitors of PDE5 prolong the NO signal, thereby increasing the widening of blood vessels and blood flow.

The men in this study were of an average age of 53.6 years and the majority of them reportedly never complained of any (facial) skin problems prior to taking these ED drugs. The men took the PDE5i ED drugs for as little as 7.5 months to 21 months. The average ED tablet intake was 3.4 tablets per week.

The men met all criteria for rosacea and other conditions that could cause a red facial appearance were ruled out. To find out if the erectile dysfunction drugs were able to induce rosacea symptoms, the men were asked to discontinue their use of ED drugs. While off the ED drugs, the men were treated with topical metronidizole for a period of 8 weeks and their rosacea cleared up except for the telangiectasias.

Three months after stopping the ED drugs, the men were asked to continue their ED treatments. A relapse of rosacea with the associated symptoms of erythema, inflammation and papules was reported for all men who re-initiated their ED treatment.

The findings reported in this study suggest a possible correlation between the use of Phosphodiesterase 5 Inhibitor drugs and the induction of rosacea. The increased production of NO following administration of PDE5 inhibitor drugs, could lead to changes in blood vessels and the development of rosacea in genetically predisposed patients. It is currently unclear whether nitric oxide is the key agent in this scenario. Previously, no association of increased amounts of NO in rosacea skin could be found by other studies.

Ioannides, D. et al. (2009) Phosphodiesterase-5 inhibitors and rosacea: report of 10 cases. Br. J. Dermatol. 160: 719-20.

As both rosacea and autism affect my family, I was wondering if a link between the two conditions existed. Chronic inflammation is one of the hallmarks of both rosacea and autism and research has suggested that processes triggered by our innate immunity are to blame for such inflammation. Innate immunity is how our body reacts to foreign microorganisms by activating specialized “killer” cells such as macrophages without the involvement of antibodies, which are part of our adaptive immune system.

Besides the inflammatory processes that play a role in the etiology of autism and rosacea, both conditions appear to have key trigger factors such as environmental factors, dietary factors and stress.

With the discovery in 2007 of a link between rosacea and antimicrobial peptides (specifically cathelicidins) that are aberrantly processed and overly abundant in rosacea skin, I wanted to find out if there were any studies done that looked at antimicrobial peptides such as cathelicidins and autism.

Cathelicidins

Cathelicidins belong to a group of antimicrobial peptides that are found in the skin and in certain white blood cells (neutrophils) and contribute to the body’s early host defense against infection. Cathelicidins are produced as inactive precursor proteins and when cleaved into activated antimicrobial peptides, destroy bacteria by disrupting the integrity of their membranes (just as most antibiotics do).

Cathelicidins are not just activated by skin injuries and invading microorganisms. The cathelicidin response is also dependent on the steroid hormone vitamin D. In addition to its effect on calcium homeostasis and bone formation, vitamin D is an important regulator of the innate immune response. Studies have shown that the cathelicidin genes are controlled by a vitamin D response element (a molecular switch if you will): when activated vitamin D levels are low (such as in the winter), in theory there will be less production of cathelicidins.

How Does Vitamin D work?

We get some of our vitamin D through our food, but the majority of active vitamin D is produced in the skin: UVB radiation from the sun is required to produce pre-vitamin D3 (calciol) from 7-hydroxycholesterol. Pre-vitamin D3 needs to be modified by 2 additional enzymes (found in skin, liver and kidneys) to generate active vitamin D3 (calcitriol).

So how does vitamin D fit in with autism?

Some people believe that since vitamin D plays such an important role in innate immunity and early brain development, that vitamin D deficiency during gestation or early childhood may contribute to the development of autism. The theory behind this is, that the increase in the number of autism cases over the last 20 years does not follow classic Mendelian inheritance. While autism has a strong genetic basis with many different genes playing a role, it is fair to say that the role these genes play in the etiology of autism could not have changed much over the last 20 years.

It may be possible that environmentally responsive genes play a much larger role in the development of conditions such as autism and that something in the environment, before or after birth, is influencing the outcome of our genotype. The rise in autism incidence over the last 20 years corresponds with increasing medical advice to stay out of the sun and use high SPF sunscreens, which may have resulted in a severe vitamin D deficiency in many people (especially during the winter months).

In addition, a strikingly high male-to-female ratio in autism can be explained by the stimulating effect estrogen has on vitamin D levels in the brain: estrogen protects female brains from calcitriol deficiencies whereas testosterone does not. Note that in rosacea there seems to be a high female-to-male ratio.

If vitamin D deficiency plays any role in autism, then symptoms should improve during the summer. Also, autism prevalence would be higher in (more) Northern latitudes. Some studies (see Cannell 2008) found an association between prevalence of autism and latitude, including recent CDC data that looked at autism prevalence in 14 states.

How can sun avoidance in the summer lead to vitamin D deficiency?

When a fair skinned adult stays in the sun for 20 minutes (full body), approximately 20,000 units of vitamin D enters their circulation. You would have to drink 200 glasses of milk or take 50 multivitamins to receive a similar amount of vitamin D.

Patients suffering from Rickets, a condition in which vitamin D deficiency is caused by a genetically defective production of the enzyme that activates vitamin D, share some of the symptoms of autism such as hypotonia and developmental delay. Children with Williams’s Syndrome, who have very high levels of vitamin D in early infancy, often show signs that are the complete opposite of autism such as overfriendliness, empathy and increased sociability.

A number of drugs can interfere with vitamin D metabolism. One of them is sodium valproate (a.k.a. Depakote), a drug that is frequently used to treat epilepsy, seizures and convulsions. Numerous animal studies have shown that sodium valproate (or valproic acid) given during pregnancy can lead to abnormal brain development and symptoms of autism in offspring. It has been shown that sodium valproate interferes with vitamin D’s actions. Sodium valproate or valproic acid is often used to generate mice that show the classic symptoms of autism.

Vitamin D and rosacea

While the available data from studies suggests a possible risk factor for autism and vitamin D deficiency, it is unclear at the present time whether vitamin D has a positive or negative effect on the outcome of rosacea.

Based on the findings of Yamasaki and colleagues, vitamin D would increase cathelicidin production, which in rosacea would lead to a higher level of (disease causing) antimicrobial peptides. However, some studies have looked at the seasonal effect of rosacea and reported that for the majority of rosacea patients, symptoms did improve during the summer months. Also, other studies have found that vitamin D deficiency is associated with increased levels of the matrix metalloproteinases (MMP 2 and 9), which are related to the serine proteases involved in rosacea. If higher levels of vitamin D could lower the levels of the serine proteases in the skin that are causing the inflammation-causing splicing of cathelicidin, then higher levels of circulating vitamin D could therefore be beneficial to the management of rosacea symptoms.

Additional Reading

Zanetti, M. (2005) The role of cathelicidins in the innate host defenses of mammals. Curr. Issues Mol. Biol. 7: 179-196.

Schauber, J. and Gallo, R.L. (2008) The vitamin D pathway: a new target for control of the skin’s immune response? Exp. Dermatol. 17: 633-39.

Cannell, J.J. (2008) Autism and vitamin D. Med. Hypotheses 70: 750-59.

Yamasaki, K. et al. (2007) Increased serine protease activity and cathelicidin promote skin inflammation in rosacea. Nat. Med. 13: 975-80.