Vitamins for ulcerative colitis

6 Need-to-Know Nutrients for Ulcerative Colitis

When you have ulcerative colitis (UC), you may not get enough of the nutrients your body needs.

Problems with how your body absorbs nutrients, as well as blood loss, diarrhea, and even the drugs used to treat this inflammatory bowel disease all can increase the risk of nutritional deficiency.

But maintaining healthy levels of essential nutrients is possible with proper nutrition and supplementation. Find out what nutritional deficiencies are most commonly associated with ulcerative colitis, and what you can do about it.

Calcium and Vitamin D Keep Bones Strong

Kristi L. King, MPH, RDN, senior pediatric dietitian at Texas Children’s Hospital and a clinical instructor at the Baylor College of Medicine in Houston, said that low stores of calcium and vitamin D are the main vitamin and mineral deficiencies in patients with ulcerative colitis. When you have colitis, “the intestines and colon don’t absorb nutrients in the same way that they do for someone without the disease,” she says, adding that many drugs commonly prescribed to treat colitis, such as prednisone, can also interfere with the absorption of calcium and vitamin D when used for prolonged periods of time.

You may not have any noticeable symptoms, but your gastroenterologist should regularly check for these deficiencies as part of ulcerative colitis treatment, King says. Over-the-counter supplements can help restore healthy levels. In serious cases, you may need very high doses at first, followed by a lower maintenance dose. Making some changes to your diet will help, too.

Dairy products are rich sources for both calcium and vitamin D, but according to a study published in October 2014 in the journal Food and Nutrition Sciences, many people with UC restrict dairy from their diets due to concerns that it will trigger symptoms. If you’re sensitive to dairy, grab a glass of soy or rice milk that’s fortified with calcium and Vitamin D instead. You can also increase your leafy green vegetables (cooked to minimize bowel irritation), which are rich in these nutrients.

Iron Helps Fight Fatigue

Iron deficiency occurs in roughly 60 to 80 percent of people with inflammatory bowel disease, affecting their quality of life, according to a review published in 2013 in the journal Annals of Gastroenterology. This deficiency may be due to blood loss from bloody diarrhea or internal ulcerations of the colon, or could be caused by some drugs used to treat ulcerative colitis, such as cholestyramine.

“Symptoms of iron deficiency include fatigue, pale skin, and a profound craving for ice or mud,” says David T. Rubin, MD, Joseph B. Kirsner professor of medicine and co-director of the Digestive Diseases Center at The University of Chicago Medical Center in Illinois.

Although it was a panacea for Popeye, Dr. Rubin says that spinach alone isn’t enough to treat iron deficiency. Options include iron supplements, though they may make ulcerative colitis symptoms worse in some people, and intravenous iron infusions, which may also be used to replenish iron stores.

Only very rarely are blood transfusions used, Rubin says. Once your iron stores are back to normal, eating an iron-rich diet with foods like lean meats and cooked leafy greens can help keep you at a healthy level.

B Vitamins Can Boost Energy and Memory

People with ulcerative colitis may have problems absorbing folate — also known as folic acid or vitamin B9 — and other B vitamins, especially vitamin B12. Vitamin B12 is absorbed in only one part of the small intestine, known as the ileum, right before it hits the colon, says King. Some medications, such as cholestyramine and sulfasalazine, can prevent B12 from being absorbed in this area and interfere with folate absorption, too.

Signs of a vitamin B deficiency are a lack of energy, balance issues, a pale tongue, and tingling in the fingers and toes. Severe cases may cause memory loss and disorientation. Once diagnosed by a blood test, folate and vitamin B12 deficiencies may be treated with supplements. But if you’re on a medication that interferes with vitamin B12 absorption, the only way to make sure you’re getting enough of the vitamin is by injection, King adds.

In conjunction with treatment, eat a diet rich in sources of B vitamins and folate, like meat, poultry, and eggs, to maintain healthy levels.

Potassium Helps Relieve Muscle Cramps

Potassium deficiency may be the result of chronic vomiting and diarrhea or from use of corticosteroids (prednisone). King says potassium deficiency comes into play with ulcerative colitis because the colon is the final place where it’s absorbed in the body. “The colon actually reabsorbs potassium, and it goes through the bloodstream that way,” she says.

Symptoms of this deficiency may include muscle cramps, irregular heartbeat, or feeling dizzy and fainting. Eating a diet high in potassium-rich foods, like bananas, cooked leafy green vegetables, and potatoes, is usually enough to correct a potassium deficiency, said King. Getting too much potassium through an over-the-counter supplement may increase the risk of heart problems.

Magnesium Can Reduce Diarrhea

Magnesium deficiency is also an issue for people with ulcerative colitis because the mineral is absorbed in the colon. Magnesium loss is also associated with chronic diarrhea.

Symptoms of magnesium deficiency include muscle twitching, irritability, and poor memory.

To treat this deficiency, you may need to take oral supplements or eat more magnesium-rich foods that you can tolerate, such as creamy peanut butter, cocoa, and seafood. Other common magnesium-rich foods, like nuts and dried fruits, may not be as easily digested. “You want to make sure to talk to your registered dietitian or doctor because too much magnesium can cause diarrhea,” says King.

Additional reporting by Amy Kraft

G&H How common is vitamin D deficiency in patients with inflammatory bowel disease?

AA Normal levels of vitamin D are approximately 30 ng/mL. Levels between 20 and 30 ng/mL are considered insufficient, and anything below 20 ng/mL is considered deficient. The prevalence of vitamin D deficiency in inflammatory bowel disease (IBD) varies in different studies, but it appears that, at least in some studies, up to 60% to 70% of people with IBD have insufficient vitamin D levels. Of these, more than half meet the threshold for deficiency, and the remainder have levels consistent with vitamin D insufficiency. However, these numbers depend upon various factors, such as the location of the study, the season of measurement, and the proportion of people who have active disease.

G&H Which seems to come first: vitamin D deficiency or IBD?

AA This question comes up very frequently and is an important chicken-or-the-egg–type dilemma. Prospective data, including studies conducted by my colleagues and I, have suggested that low vitamin D levels may precede the diagnosis of IBD. In one study, women who had low levels of vitamin D had an increased risk of developing Crohn’s disease over the subsequent 2 decades. Thus, while active IBD has been associated with low vitamin D levels, it does not appear that having a diagnosis of IBD entirely explains the prevalence of vitamin D deficiency seen in this cohort. Other studies have looked at people with a relatively new diagnosis of IBD, who have had symptoms for comparatively short durations of time, and have found a high prevalence of low vitamin D levels. Laboratory experiments in various mice models have also shown that animals are more susceptible to colitis and that such colitis can be treated by vitamin D supplementation. These findings suggest, in my opinion, that there is at least a significant component of vitamin D deficiency perhaps contributing to the development of IBD; vitamin D deficiency is not purely a consequence of prolonged, undertreated IBD or bowel damage.

However, it should be noted that as people have more active disease and have a longer duration of IBD, several factors—including reduction in physical activity, alteration in diet, and changes in the intestinal absorption of vitamin D—can contribute to making patients more susceptible to vitamin D deficiency as a consequence of IBD. Therefore, I believe that there is likely a bidirectional relationship in which IBD and its consequences can cause a patient to have low levels of vitamin D, and in which having a low vitamin D level itself can affect a patient’s immune response and predispose the patient to having IBD or having a relapse of his or her IBD.

G&H Is vitamin D deficiency more common in Crohn’s disease than in ulcerative colitis?

AA The data are not very clear on this issue. Certainly, more associations have been described between vitamin D and Crohn’s disease than with ulcerative colitis, so there does seem to be a link favoring Crohn’s disease in terms of pathogenesis and relapse. However, there does also seem to be an association between ulcerative colitis disease activity and vitamin D. Several studies have shown that vitamin D levels are low in people with ulcerative colitis and in those with Crohn’s disease who do not have much small bowel involvement.

G&H How does vitamin D affect the severity of IBD or its complications?

AA A growing body of literature has linked disease severity to low vitamin D levels. For example, my colleagues and I looked at a cohort of nearly 3000 people with Crohn’s disease or ulcerative colitis and examined vitamin D levels and future risk of surgery and hospitalizations. We were able to show that there clearly is a gradation in the risk of surgery in people who had normal, insufficient, and deficient levels of vitamin D. People who had insufficient levels of vitamin D (20-30 ng/mL) had a higher risk of surgery and hospitalization, and people with levels lower than 20 ng/mL had an even higher risk of surgery and hospitalization. Other studies have similarly shown that people with higher disease activity tend to be low in vitamin D, and the risk of surgery and hospitalization tends to be higher in those who are deficient compared to those who are not, suggesting a link between vitamin D levels and the risk of surgery and hospitalization.

My colleagues and I have also performed studies showing that low vitamin D levels may have an influence on IBD, not just through an effect on disease activity but on other complications as well. Vitamin D can be considered a hormone with a number of effects on the immune system that are responsible for mediating susceptibility to infections and perhaps malignancy. Studies have suggested that vitamin D levels may be important in how patients respond to pathogens. Studies have linked low vitamin D levels with an increased risk of cancer, particularly colon cancer, in people with IBD. It has also been shown that low vitamin D levels are linked to a higher risk of Clostridium difficile infection in the IBD population, which is a significant problem in these patients.

Although some of these data are preliminary, there are laboratory mechanisms supporting the biological poss­ibility of each of these associations. Nevertheless, further studies are needed to demonstrate the consistency of these associations before embarking on therapeutic trials.

G&H Can vitamin D supplementation help prevent relapse or maintain remission in patients with IBD?

AA Several studies have looked at whether vitamin D supplementation keeps Crohn’s disease in remission. A Scandinavian study randomized people with Crohn’s disease in remission to vitamin D or placebo. At the end of the year, there was a tendency toward lower rates of relapse in people treated with vitamin D compared with placebo. The relapse rate in the vitamin D arm was 13% compared with 29% in patients who received placebo, suggesting that vitamin D may play a role in preventing relapse.

Other studies have looked at vitamin D levels during remission and have suggested that there is a higher risk of relapse in patients with low vitamin D levels. For example, in a study by Gubatan and colleagues, patients in clinical remission with vitamin D levels below 35 ng/mL had a 25% greater risk of relapse over the subsequent 12 months, independent of even endoscopic and histologic activity.

G&H Has there been any research specifically on the effect of vitamin D on disease activity?

AA Very small studies (of 18-20 people) have shown that vitamin D supplementation is associated with improvements in disease activity as well as health-related quality of life. We are just starting to see emerging therapeutic trials of vitamin D supplementation with disease activity as an endpoint. Most studies thus far have looked at bone density as an endpoint because we have been used to thinking of vitamin D as affecting bone density and bone health. However, these emerging data suggest that there should be a focus on the more systemic effects of vitamin D.

G&H Should all IBD patients, including children, receive vitamin D supplementation?

AA All IBD patients, including children, should be assessed for vitamin D deficiency through measurement of 25-hydroxy vitamin D in their blood. In my practice, I do this once a year in all patients. Any patients who have insufficient or deficient levels should receive vitamin D supplementation. Adverse events linked to normal vitamin D supplementation and restoration of normal levels are rare. Of course, clinicians should be aware that taking extremely high levels of vitamin D (several times above normal) may cause adverse effects.

G&H What dose is appropriate in IBD patients?

AA The dose depends on whether a patient is insufficient or deficient in vitamin D. For patients with mild insufficiency, I recommend approximately 1000 to 2000 units of vitamin D per day. In patients who are more deficient, I tend to recommend higher doses, between 2000 and 4000 units daily, until patients develop sufficient levels, at which time I recommend 1000 units per day for maintenance. For many patients with levels of vitamin D less than 20 ng/mL, and certainly less than 15 ng/mL, I use high-dose weekly vitamin D supplementation. For example, ergocalciferol (50,000 units weekly) can be used for 10 weeks to 3 months to get vitamin D levels back to normal.

G&H Should patients taking anti–tumor necrosis factor agents receive vitamin D supplementation to improve response?

AA My colleagues and I, as well as other researchers, have shown that people who are starting anti–tumor necrosis factor (TNF) therapy who are vitamin D–deficient may have lower rates of response or earlier therapy cessation. Whether vitamin D deficiency is a marker of severity influencing response to anti-TNF therapy or whether this is a direct effect of vitamin D augmenting response to these agents is unclear. Thus, I would not recommend vitamin D supplementation just because patients are starting anti-TNF therapy. However, given the possible links between vitamin D and IBD, it may be helpful to supplement vitamin D, although this has not been proven experimentally. At the same time, it is important not to rely on supplementation as the only intervention.

G&H Is vitamin D supplementation as effective as increasing dietary vitamin D?

AA Yes. Both sources of vitamin D, either through supplementation or through diet, are effective. However, increasing dietary intake of vitamin D can sometimes be difficult, particularly in people with IBD who have food sensitivities and gastrointestinal intolerance to dairy products, which are high in vitamin D. Therefore, in many patients, supplementation ends up being the default oral route of vitamin D replacement.

G&H What other vitamin or mineral supplementation is often needed in IBD patients?

AA IBD patients are at an increased risk for a number of vitamin and mineral deficiencies. Vitamin D, iron, and vitamin B12 are frequently low in patients with IBD and, in my opinion, are the most clinically relevant deficiencies in these patients; thus, these 3 nutrients should be systematically measured periodically in patients with IBD. Iron, in particular, is important because people with low iron levels have a lower quality of life, as the deficiency impacts their energy levels.

There are also other micronutrients that may be deficient in patients with IBD. For example, zinc seems to be deficient in IBD patients, although we do not fully understand the implications of this deficiency yet. Clinicians should keep an open mind for deficiencies of other vitamins as well.

G&H What are the next steps in research?

AA The most important next step is to further evaluate the bidirectional relationship of vitamin D deficiency and IBD to definitively determine which one comes first. Because prolonged bowel damage can cause IBD, I think we should not dismiss IBD as merely being a consequence of vitamin D deficiency, particularly with growing evidence and laboratory data suggesting that vitamin D is a potential mediator of several immune responses. I think it is important to understand the role of vitamin D in the treatment of IBD itself, and not just for the treatment of vitamin D deficiency. In particular, this requires rigorous interventional trials that aim to replete vitamin D levels to normal, with disease activity as an endpoint.

We also need to better understand the optimal dose of vitamin D supplementation, and whether there are factors such as genetics that influence response to such supplementation. It is also important to define what the optimal vitamin D level should be in patients with IBD, and whether there should be a different adequate level when looking at inflammation as an endpoint.

G&H Are there any ongoing or upcoming studies in this area that you are anticipating?

AA There are many studies that are just starting to look at vitamin D as a therapeutic intervention in various clinical settings in Crohn’s disease and ulcerative colitis. Specifically, studies are examining the role of vitamin D in the induction and maintenance of remission; in conjunction with other therapies, such as anti-TNF agents; and in the prevention of postoperative recurrence. Clinicians are eagerly awaiting data from these studies to help guide clinical practice.

Dr Ananthakrishnan has no relevant conflicts of interest to disclose.

Suggested Reading

Ananthakrishnan AN. Editorial: vitamin D and IBD: can we get over the “causation” hump? Am J Gastroenterol. 2016;111(5):720-722.

Ananthakrishnan AN, Cagan A, Gainer VS, et al. Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn’s disease. Inflamm Bowel Dis. 2013;19(9):1921-1927.

Ananthakrishnan AN, Cheng SC, Cai T, et al. Association between reduced plasma 25-hydroxy vitamin D and increased risk of cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014;12(5):821-827.

Ananthakrishnan AN, Khalili H, Higuchi LM, et al. Higher predicted vitamin D status is associated with reduced risk of Crohn’s disease. Gastroenterology. 2012;142(3):482-489.

Gubatan J, Mitsuhashi S, Zenlea T, Rosenberg L, Robson S, Moss AC. Low serum vitamin D during remission increases risk of clinical relapse in patients with ulcerative colitis . Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2016.05.035.

The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status

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Forvia

What is Forvia?

FORVIA is a multivitamin/mineral product that provides nutritional support for patients who have a reduced ability to absorb vitamins and minerals from diet because of gastrointestinal conditions such as:

  • Inflammatory bowel disease (IBD)
  • Crohn’s disease
  • Ulcerative colitis
  • Celiac disease
  • Other malabsorption conditions including weight loss and other gastrointestinal surgeries.

FORVIA tablets and chewables were developed on the basis of growing medical knowledge about the effects of disease on the body’s ability to absorb and use nutrients. The vitamins and minerals we selected for this nutritional supplement were based on current clinical findings about the common nutritional deficiencies and daily vitamin and mineral needs for patients who have malabsorption. The innovators at Forvia also researched ingredients found in other vitamin and nutrient supplements on the market, which helped us determine what ingredients to not include in our formula. Some of these ingredients actually prevent the important nutrients from being absorbed into the body, and can aggravate symptoms of other medical conditions. Our goal was to make ours one of the best health supplements you can buy.

FORVIA contains the fat-soluble vitamins A, D, E, and K in water-miscible form to enable optimal absorption and efficiency. People with malabsorption conditions from disease or weight loss surgery have an increased risk for low levels of these vitamins. Vitamin D, which is important for maintaining bone mass, is supplemented at two times the daily value because it is not optimally absorbed by people with IBD or who have undergone gastric bypass surgery.FORVIA contains folic acid, which has been found in a number of studies to be associated with a reduced risk for the development of colorectal cancer or dysplasia in individuals with ulcerative colitis.

FORVIA contains vitamin C and iron in the ratio and amounts shown to increase iron absorption when given together. Iron is provided as ferrous fumarate, which is highly soluble in the gastrointestinal tract, is well-tolerated orally, and was less toxic than ferrous sulfate or ferrous gluconate in laboratory studies.

FORVIA contains 1000 mcg of vitamin B12 (cyanocobalamin). B12 in the diet may be poorly absorbed in patients with IBD, particularly in extensive Crohn’s disease, or malabsorption from other diseases or from surgery. However, a large oral dose as in FORVIA allows sufficient B12 to be absorbed and eliminate the need for injections.

FORVIA contains zinc, important for wound healing and immune function, at 150% of the Daily Value because zinc may be lost through increased excretion in individuals with IBD.

FORVIA contains calcium diphosphate, a “non-gassy”/non-carbonate form of calcium for improved bone health.FORVIA does not contain magnesium as an active ingredient because magnesium can promote diarrhea.

FORVIA is lactose-free and gluten-free (important for people allergic to gluten due to celiac disease), and contains no dyes, artificial sweeteners, or flavorings.

FORVIA chewables are adult chewable vitamins that provide an alternative for those who can’t easily swallow tablets. The natural orange-flavored chewables have the same multivitamin and mineral content as the tablets, and are a convenient choice for people who may have difficulty swallowing tablets or who have an ostomy or other surgeries. Our chewable calcium supplements may be a good choice for people with gastric bypass procedures who need high-potency supplementation. See the Complete Product and Use Information for a full description of active ingredients.

FORVIA is a non-prescription product. However, taking FORVIA daily is one component of a comprehensive medical and nutritional program. Patients are urged to consult their physician about their individual treatment program and discuss the role of FORVIA in meeting their individual nutritional needs.

FORVIA tablets and chewables are manufactured in modern U.S. facilities using the highest quality ingredients and are inspected and laboratory-tested to assure compliance with specifications before leaving the factory. Our confidence in the quality of our product is reflected in our money-back guarantee.

What Forvia Can Help With

As we mentioned above, Forvia can help with several kinds of inflammatory bowel diseases and gastrointestinal disorders that are known to cause discomfort as well as major health issues. Because Forvia is designed to be highly absorbable, our IBD supplement can help those who have a hard time absorbing all of the essential nutrients their bodies need to heal get proper supplementation. Keep reading to see some of the diseases and disorders our IBD supplements can help with, or browse our online store and get Forvia today.

Crohn’s Disease

An inflammatory bowel disease, Crohn’s disease can cause numerous problems in a person’s body. Crohn’s is considered an autoimmune disease, meaning that you don’t contract this disease from contact, ingestion, or by breathing it in, but rather from your own immune system mistakenly “attacking” your own body. Crohn’s disease can cause mild to severe inflammation of your digestive tract, either in one specific area or causing problems in many different areas. This IBD can lead to mild to severe abdominal pain, diarrhea, fatigue, and other health issues.

Because Crohn’s disease affects the immune system, you may not be able to absorb essential nutrients your body needs to function or heal. Forvia can help you get the nutrients your body needs to operate properly. Learn more about our Crohn’s disease supplements and see what Forvia can do for you!

Ulcerative Colitis

UC is very similar to Crohn’s disease. Both are considered inflammatory bowel diseases as well as autoimmune diseases. Both UC and Crohn’s affect the immune system, however ulcerative colitis is usually only present in the innermost lining of your large intestine. Similar to Crohn’s, UC can cause mild to severe inflammation in your digestive tract, including the formation of ulcers along the surface or just under the lining of your large intestine. This IBD can also cause symptoms similar to Crohn’s disease, which makes seeing your doctor if you experience any of them extremely important.

UC can also make it hard or even impossible for your body to absorb all of the essential nutrients your body needs. Because Forvia is one of the most easily absorbable IBD supplements on the market, you could help your body get all of the nutrients it needs to operate normally. Learn more about our ulcerative colitis supplements and see how Forvia can help you!

Celiac Disease

While it’s still considered an autoimmune disease, celiac disease is different from both Crohn’s disease and ulcerative colitis. All three affect the immune system, but celiac disease is brought on by a sensitivity to gluten, which is a protein found in wheat, barley, and rye. While all inflammatory bowel diseases affect people differently, celiac disease may be present in someone their entire lives and only pop up at a single moment. It’s also one of the only IBDs that’s caused by sensitivity to certain foods. Symptoms are similar to UC and Crohn’s disease, but can usually be avoided or mitigated by abstaining from foods that contain gluten.

Even if you stay away from foods with gluten, it can be difficult for your body to absorb vital nutrients that your body depends on. Forvia can help provide the nutrients your body needs to heal, helping to improve your overall quality of life. Learn more about our celiac disease supplements and what they can do for you.

Bariatrics

Bariatric surgery can help people achieve their preferred overall weight. While most weight loss surgeries are designed to help people achieve their weight goals, they can also cause major health issues that don’t always make the surgery worth the end results. Stomach and gastrointestinal issues, including chronic mild to severe nausea, bleeding, and an inability to digest vital nutrients can all occur after weight loss surgeries. These symptoms can differ depending on your specific surgery as well as the severity to which you’ve changed your body.

If you’re having problems digesting and absorbing essential nutrients after your bariatric surgery, then Forvia may just be the perfect supplement for you. Learn more about our bariatric supplements and see if Forvia is right for you!

Forvia is one of the best IBD supplements and post bariatric surgery supplements around. Before you order Forvia though, we encourage you to speak with your doctor or healthcare provider to make sure that our supplement is right for you. Learn more about our Forvia supplements to see how they can help you and if they’ll be able to benefit you.

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A role for B 12 in inflammatory bowel disease patients with suppurative dermatoses? An experience with high dose vitamin B 12 therapy

2.2 Patient 2

A 58 year old woman presented with a 36 year history of hidradenitis suppurativa of the buttocks, inguinal and pubic regions and the diagnosis was confirmed by a dermatologist. Five years earlier she had a subacute presentation over three months culminating in a diagnosis of colonic, duodenal and perianal Crohn’s disease. At that time she developed diarrhoea admixed with blood and inflammatory polyarthropathy with ankle swelling and perianal disease. Ileocolonoscopy revealed large chronic ulcers with skip lesions affecting the colon and at that time a normal ileum. A duodenal biopsy revealed acute on chronic inflammation and granuloma formation. The perianal region revealed thickened skin tags with painless fissuring and perianal fistulous tract openings. The disease was treated with parenteral and then tapering oral corticosteroids, a course of metronidazole and maintenance azathioprine (1.7 mg/kg). Subsequent colonoscopies disclosed only occasional aphthous ulcers of the ileum two years later and four years later a normal ileum but occasional aphthous ulcers in the colon. She had two sisters with attenuated forms of hidradenitis suppurativa and two nephews diagnosed with Crohn’s disease at ages 14 and 24.

The typical perianal Crohn’s disease cleared within months of her treatment with immunosuppression but her vulval and buttock hidradenitis suppurativa continued unabated as it had for 36 years. In the past, treatments with oral and topical antibiotics and isotretinoin failed to alter the course of the condition. Despite normal vitamin B 12 indices, an empiric trial of 1000 μg vitamin B 12 IM fortnightly for six weeks and then monthly produced an improvement resulting in minimal new hidradenitis eruptions. In winter months she was able to extend dosing to every six weeks but in summer extension beyond a month led to breakthrough of the condition and new eruptions. The response to the vitamin B 12 therapy is sustained over three years up to writing this report.

2.3 Other patients

The reasons for trying B 12 in the first two cases were several-fold: (i) the dermatology literature suggested a role for this treatment in some dermatoses, (ii) the safety profile of B 12 was known to be excellent, and (iii) B 12 is an economical off-patent therapy. On the basis of the very positive experience with the first two cases, high dose vitamin B 12 was used in an open label experience with another ten IBD patients without biochemical evidence of B 12 deficiency attending our clinic, who had clinical evidence of inflammatory or suppurative perianal, perineal and buttock dermatoses. All patients were out of hospital and the vitamin B 12 was administered either in the IBD clinic or by the patient’s family physician. A dose of 1000 μg hydroxocobalamin chloride or cyanocobalamin IM was administered at intervals of two weeks for six weeks and then monthly thereafter. These patients were followed for a median 46 weeks (range 24–68). Beneficial outcomes were witnessed in six of the patients with a variety of suppurative skin conditions ( Table 1 ). In the successful cases vitamin B 12 appeared to give additional benefit as stable doses of concomitant therapies had been instituted greater than six months prior to vitamin B 12 therapy. An additional two patients (cases 7, 12) had improvements which could be attributed to concomitant medication ( Table 1 ).

3 Discussion

Hidradenitis suppurativa can present with perianal disease findings indistinguishable from perianal Crohn’s disease and remains an important but not always appreciated differential diagnosis. Many case reports of the two diseases occurring together and familial associations with both diseases support a common disorder of immune regulation. 17 – 22 Suppression of TNFα with infliximab has therapeutic benefit in patients suffering from Crohn’s disease, hidradenitis suppurativa and both conditions occurring together 23 – 28 supporting the hypothesis of a common inflammatory pathway in these diseases.

While suppurative skin conditions do not rate mention in the classic descriptions of vitamin B 12 deficient patients and reduced l -methylmalonyl-coA mutase activity in children with methylmalonic acidemia does not predispose to inflammatory skin disorders, there are several lines of evidence to suggest that high dose vitamin B 12 can modulate inflammation. One theory is that S-adenosy- l -methionine may be reduced in some patients with normal B 12 due to reduced methionine synthase activity. S-adenosy- l -methionine has been shown to reduce serum TNFα levels in rats treated with lipopolysaccahride (LPS) and reduce TNFα production by LPS treated murine macrophages. 29 Research into the neurological manifestations of vitamin B 12 deficiency has uncovered remarkable alterations in both cerebrospinal fluid (CSF) and systemic cytokines. Adult cobalamin deficient patients have high TNFα and low epidermal growth factor (EGF) in both serum and CSF, which normalise with cobalamin treatment. 30 As an interesting aside, EGF receptor inhibitors developed as cancer therapies have as side effects a wide variety of skin lesions including acneiform folliculitis. 31

In summary, the two index cases had excellent responses, which we attribute to high dose B 12 treatment. This and the open labelled experience in a further consecutive series of IBD patients with perianal suppurative disorders raise the possibility of high dose, frequent vitamin B 12 as an adjunct treatment in IBD patients with suppurative dermatoses. Our experience is supported by randomised control trials of high dose, daily topical vitamin B 12 therapy in some skin disorders 13 and oral administration for oral aphthous ulceration. 11 The effect does not appear to be a function of measurable vitamin B 12 deficiency. The mechanism may involve vitamin B 12 -mediated immunomodulation of TNFα and EGF.

The use of vitamin B 12 in our patients was open label and concomitant therapies in many of the cases may have provided benefit. Future studies would be strengthened by biopsy designated dermatological diagnosis notwithstanding concerns of pathergy. Further clinical trials in patients with biopsy-characterised suppurative dermatoses, including hidradenitis suppurativa, associated with inflammatory bowel disease are needed to properly define the role of this therapy.

Acknowledgements

The authors thank Julia O’Brien MD for her help with German translation of source articles. MM was the recipient of a Ferring Australia IBD clinician establishment award.

1 Sandborn W.J. Fazio V.W. Feagan B.G. Hanauer S.B. American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn’s disease Gastroenterology 125 2003 1508 – 1530 2 Satsangi J. Silverberg M.S. Vermeire S. Colombel J.F. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications Gut 55 2006 749 – 753 3 Alikhan A. Lynch P.J. Eisen D.B. Hidradenitis suppurativa: a comprehensive review J Am Acad Dermatol 60 2009 539 – 561 4 Braverman I.M. Skin signs of gastrointestinal disease Gastroenterology 124 2003 1595 – 1614 5 Polysangam T. Heubi J.E. Eisen D. Balisteri W.F. Lucky A.W. Cutaneous Crohn’s disease in children J Am Acad Dermatol 36 1997 697 – 704 6 Magro C.M. Crowson A.N. Sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive cutaneous reaction pattern reflecting systemic disease J Cutan Pathol 25 1998 215 – 221 7 Tefferi A. Pruthi R.K. The biochemical basis of cobalamin deficiency Mayo Clin Proc 69 1994 181 8 Scalabrino G. Cobalamin (vitamin B 12 ) in subacute combined degeneration and beyond: traditional interpretations and novel theories Exp Neurol 192 2005 463 – 479 9 Green R. Indicators for assessing folate and vitamin B 12 status and for monitoring the efficacy of intervention strategies Food Nutr Bull 29 2008 S52 – S66 10 Selhub J. Jacques P.F. Dallal G. et al. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B 12 status Food Nutr Bull 29 2008 S67 – S73 11 Volkov I. Rudoy I. Freud T. et al. Effectiveness of vitamin B 12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial J Am Board Fam Med. 22 2009 9 – 16 12 Volkov I. Press Y. Rudoy I. Vitamin B 12 could be a “master key” in the regulation of multiple pathological processes J Nippon Med Sch 73 2006 65 – 69 13 Stucker M. Pieck C. Stoerb C. Niedner R. Hartung J. Altmeyer P. Topical vitamin B 12 —a new therapeutic approach in atopic dermatitis—evaluation of efficacy and tolerability in a randomized placebo controlled multicentre clinical trial Br J Dermatol 150 2004 977 – 983 14 Niemand-Anderssen I. A new method in seborrhic skin diseases. Dermatol Wochenschr 126 1952 834 – 841 15 Blut F. Experience with vitamin B 12 in the treatment of dermatoses, particularly of seborroic origin Med Klin (Munich) 49 33 1954 1293 – 1294 16 Simon S.W. Vitamin B 12 therapy in allergy and chronic dermatoses J Allergy 22 1951 183 – 185 17 Tsianos E.V. Dalekos G.N. Tzermias C. Merkouropoulos M. Hatzis J. Hidradenitis suppurativa in Crohn’s disease. A further support to this association J Clin Gastroenterol 20 1995 151 – 153 18 Church J.M. Fazio V.W. Lavery I.C. et al. The differential diagnosis and comorbidity of hidradenitis suppurativa and perianal Crohn’s disease Int J Colorect Dis 8 1993 117 – 119 19 Attanoos R.L. Appleton M.A. Hughes L.E. Ansell I.D. Douglas-Jones A.G. Williams G.T. Granulomatous hidradenitis suppurativa and cutaneous Crohn’s disease Histopathology 23 1993 111 – 115 20 Gower-Rousseau C. Munoury V. Colombel J.F. et al. Hidradenitis suppurativa and Crohn’s disease in two families: a significant association? Am J Gastroenterol 87 1992 928 21 Burrows N.P. Jones R.R. Crohn’s disease in association with hidradenitis suppurativa Br J Dermatol 126 1992 523 22 Ostlere L.S. Langtry J.A. Mortimer P.S. Straughton R.C. Hidradenitis suppurativa in Crohn’s disease Br J Dermatol 125 1991 384 – 386 23 Gonzalez-Lama Y. Lopez-San R.A. Marin-Jimenez I. et al. Open-label infliximab therapy in Crohn’s disease: a long term multicentre study of efficacy, safety and predictors of response Gastroenterol Hepatol 31 2008 421 – 426 24 Moschella S.L. Is there a role for infliximab in the current therapy of hidradenitis suppurativa? A report of three treated cases Int J Dermatol 46 2007 1287 – 1291 25 Rosi Y.L. Lowe L. Kang S. Treatment of hidradenitis suppurativa with infliximab in a patient with Crohn’s disease J Dermatolog Treat 16 2005 58 – 61 26 Lebwohl B. Sapadin A.N. Infliximab for the treatment of hidradenitis suppurativa J Am Acad Dermatol 49 5 Suppl 2003 S275 – S276 27 Katsanos K.H. Christodoulou D.K. Tsianos E.V. Axillary hidradenitis suppurativa successfully treated with infliximab in a Crohn’s disease patient Am J Gastroenterol 97 2002 2155 – 2156 28 Martinez F. Nos P. Benlloch S. et al. Hidradenitis suppurativa and Crohn’s disease: response to treatment with infliximab Inflamm Bowel Dis 7 2001 323 – 326 29 Watson W.H. Zhao Y. Chawla R.K. S-Adenosylmethionine attenuates the lipopolysaccharide-induced expression of the gene for tumour necrosis factor α Biochem J 342 1999 21 – 25 30 Scalabrino G. Peracchi M. New insights into the pathophysiology of cobalamin deficiency TRENDS in Mol Med 12 2006 247 – 254 31 Duvic M. EGFR inhibitor-associated acneiform folliculitis: assessment and management Am J Clin Dermatol 9 2008 285 – 294

Tables

Table 1

Patient Age/sex Diagnosis Perianal fistula Dermatoses Extraintestinal manifestations Response Concomitant therapy
1 41 F a IBD-U y Folliculitis, perineal nodules Sacroileitis, iritis Complete resolution TP then cease
2 61 F a CD L2L4B1 n HS b Erythema nodosum Complete resolution TP
3 31 F PD y Nil Nil No response TP/aTNFα
4 43 M PD y Nil Nil No response TP/aTNFα
5 23 F CD L1B1 y HS c Nil Complete resolution TP/aTNFα
6 18 F UC E3S2 n Spongiotic dermatitis b Suppurative folliculitis b Nil Complete resolution TP
7 34 M CD L3B1 n Acneiform rash d Nil Partial resolution TP/GCS
8 15 M CD L2B1 n Pustular eruption Nil Complete resolution TP
9 27 F Behcet’s n Vulval ulcers Nil No response nil
10 48 F PD y Cellulitis and furunculosis Nil Complete resolution TP/aTNFα then ceased
11 28 M CD L1B3 y Pustular eruption Nil No response TP/aTNFα
12 38 M CD L3 y HS d Nil Partial resolution TP/aTNFα
Patient Age/sex Diagnosis Perianal fistula Dermatoses Extraintestinal manifestations Response Concomitant therapy
1 41 F a IBD-U y Folliculitis, perineal nodules Sacroileitis, iritis Complete resolution TP then cease
2 61 F a CD L2L4B1 n HS b Erythema nodosum Complete resolution TP
3 31 F PD y Nil Nil No response TP/aTNFα
4 43 M PD y Nil Nil No response TP/aTNFα
5 23 F CD L1B1 y HS c Nil Complete resolution TP/aTNFα
6 18 F UC E3S2 n Spongiotic dermatitis b Suppurative folliculitis b Nil Complete resolution TP
7 34 M CD L3B1 n Acneiform rash d Nil Partial resolution TP/GCS
8 15 M CD L2B1 n Pustular eruption Nil Complete resolution TP
9 27 F Behcet’s n Vulval ulcers Nil No response nil
10 48 F PD y Cellulitis and furunculosis Nil Complete resolution TP/aTNFα then ceased
11 28 M CD L1B3 y Pustular eruption Nil No response TP/aTNFα
12 38 M CD L3 y HS d Nil Partial resolution TP/aTNFα

a

Index cases.

b

Histopathological confirmation.

c

Appeared to get better with addition of B 12 (HS persisted during 6 months of anti-TNFα).

d

Response could have been related to other medication.

Table 1

Patient Age/sex Diagnosis Perianal fistula Dermatoses Extraintestinal manifestations Response Concomitant therapy
1 41 F a IBD-U y Folliculitis, perineal nodules Sacroileitis, iritis Complete resolution TP then cease
2 61 F a CD L2L4B1 n HS b Erythema nodosum Complete resolution TP
3 31 F PD y Nil Nil No response TP/aTNFα
4 43 M PD y Nil Nil No response TP/aTNFα
5 23 F CD L1B1 y HS c Nil Complete resolution TP/aTNFα
6 18 F UC E3S2 n Spongiotic dermatitis b Suppurative folliculitis b Nil Complete resolution TP
7 34 M CD L3B1 n Acneiform rash d Nil Partial resolution TP/GCS
8 15 M CD L2B1 n Pustular eruption Nil Complete resolution TP
9 27 F Behcet’s n Vulval ulcers Nil No response nil
10 48 F PD y Cellulitis and furunculosis Nil Complete resolution TP/aTNFα then ceased
11 28 M CD L1B3 y Pustular eruption Nil No response TP/aTNFα
12 38 M CD L3 y HS d Nil Partial resolution TP/aTNFα
Patient Age/sex Diagnosis Perianal fistula Dermatoses Extraintestinal manifestations Response Concomitant therapy
1 41 F a IBD-U y Folliculitis, perineal nodules Sacroileitis, iritis Complete resolution TP then cease
2 61 F a CD L2L4B1 n HS b Erythema nodosum Complete resolution TP
3 31 F PD y Nil Nil No response TP/aTNFα
4 43 M PD y Nil Nil No response TP/aTNFα
5 23 F CD L1B1 y HS c Nil Complete resolution TP/aTNFα
6 18 F UC E3S2 n Spongiotic dermatitis b Suppurative folliculitis b Nil Complete resolution TP
7 34 M CD L3B1 n Acneiform rash d Nil Partial resolution TP/GCS
8 15 M CD L2B1 n Pustular eruption Nil Complete resolution TP
9 27 F Behcet’s n Vulval ulcers Nil No response nil
10 48 F PD y Cellulitis and furunculosis Nil Complete resolution TP/aTNFα then ceased
11 28 M CD L1B3 y Pustular eruption Nil No response TP/aTNFα
12 38 M CD L3 y HS d Nil Partial resolution TP/aTNFα

a

Index cases.

b

Histopathological confirmation.

c

Appeared to get better with addition of B 12 (HS persisted during 6 months of anti-TNFα).

d

Response could have been related to other medication.

© 2010 European Crohn’s and Colitis Organisation

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