Celiac Disease and Gluten—What is the Connection?

What is celiac disease?

Celiac disease is an autoimmune condition where the intake of gluten causes the body’s immune system to attack the healthy lining of the small intestine.¹ Celiac disease is also known as gluten-sensitive enteropathy, celiac sprue, and nontropical sprue.² Celiac disease is a type of gluten-related disorder. Other gluten-related disorders include non-celiac gluten sensitivity and wheat allergy.³

How common is celiac disease?

Celiac disease occurs mostly in Caucasians of European descent and is estimated to affect approximately 0.5% to 1% of population worldwide.^4,5 Celiac disease is relatively rare among those of Chinese, Japanese, Korea, and African heritage.⁵ The disease can occur in people of any age and is 2 to 3 times more common in women than men. Celiac disease is hereditary and the incidence (which is the number of newly diagnosed cases of a disease) is approximately 5% to 10% in first-degree relatives of patients with celiac disease.^2,4,7

What is gluten? How does it cause celiac disease? 

Gluten is a protein that can be found in wheat, rye, or barley, as well as the many foods made with these grains. Gluten can also be found in oats that may be contaminated with wheat, rye, or barley during processing. Some medications may also contain gluten.^{1, 2}

Celiac disease occurs in individuals who have a sensitivity to gluten due to their genetic makeup. The body’s immune system usually acts to protect the body from disease and infections. However, in celiac disease, the ingestion of gluten by susceptible individuals causes the body’s immune response to abnormally produce antibodies and other substances that damage the cells lining the small intestine, adversely affecting the small intestine’s role in nutrient absorption from food.⁶  This increases the risk of nutritional deficiencies and other complications such as fatigue, anemia (low red blood cell count), and osteoporosis.^1,2 In addition, celiac disease has been found to be associated with a severe skin rash known as dermatitis herpetiformis and other conditions such as diabetes mellitus type 1 and thyroiditis.^1,4

What are the symptoms of celiac disease?

The presentation of celiac disease is wide-ranging and has been likened to “an iceberg”, with a small group of individuals with classic disease who present with symptoms of malabsorption, diarrhea, and weight loss; and a larger group of individuals who may only display minor gastrointestinal symptoms and other nongastrointestinal-related symptoms such as anemia, osteopenia, infertility, and neurological symptoms (atypical celiac disease). Many individuals with celiac disease may experience no symptoms at all (silent celiac disease).^4,7 

The symptoms of celiac disease can include^1,2,7,8:

§  Gastrointestinal symptoms (abdominal bloating, pain, gas, diarrhea)

§  Weight loss

§  Severe skin rash

§  Anemia

§  Joint and bone pain

§  Tingling and numbness in the fingers or legs

How is celiac disease diagnosed?

Your healthcare provider will first ask you about your symptoms and medical history. Other diagnostic tests include the following:

§  Blood tests. Blood tests are done to check the level of specific antibodies in your blood. In celiac disease, there are specific antibodies that will be elevated. It is important to remain on a gluten-rich diet (or your normal diet) when this blood test is performed. Otherwise, the antibody levels may become undetectable after a gluten-free diet is started.^1,2,7  Other blood tests may also be done to evaluate for deficiencies in iron, folate, calcium, and vitamin D.

§  Small intestinal biopsy. A small intestinal biopsy is performed when an individual tests positive for the specific antibodies in their blood test. A small sample of tissue will be removed from the small intestines by means of a small, flexible tube inserted through the mouth. The sample of tissue will then be examined under the microscope to look for changes characteristic of celiac disease in the small intestine tissue.^1,2,7

How is celiac disease treated?

Implementation of a gluten-free diet

Treatment of celiac disease requires implementation of a gluten-free diet where products containing wheat, barley, and rye are removed from the diet for life to avoid exposure to dietary gluten.^1,2 Approximately 70% of individuals experience improvement in their symptoms within 2 weeks of starting a gluten-free diet.⁹ The Table below lists examples of gluten-free foods.¹⁰

Table. List of gluten-free foods.¹⁰

Grains, flours and other starch-containing food		Other foods
Beans/ bean flours Buckwheat Corn/ corn flours Flaxseed Legumes Millet Nuts/ nut flours	Potatoes, potato starch/ flour Quinoa Rice Soy Tapioca/ tapioca starch Wild rice	Fruits Vegetables Meat and poultry Fish and seafood Dairy products

The complete elimination of gluten from the diet may be difficult as many processed foods use wheat in their manufacture. Thus, working with a dietitian can be beneficial to help find out about places to purchase gluten-free foods, cooking methods, and lifestyle resources to maintain a balanced, gluten-free diet. Individuals are encouraged to read labels on processed foods with care to determine if the food product contains wheat, barley, or rye.⁷

Although there is evidence that celiac patients can tolerate moderate quantities of oats (about 50 g per day), oats are frequently contaminated with wheat during their manufacture.⁶  Thus, it is recommended for patients newly diagnosed with celiac disease to avoid oats until symptoms resolve through a gluten-free diet. After symptoms have been controlled, up to 2 oz of oats from a reliable, uncontaminated source can be eaten daily and continued if symptoms do not return.²

Distilled alcoholic beverages such as wines are gluten-free unless gluten-containing flavorings are added after production. It is important to note that malt beverages such as beer, lager, ale, and stouts are not considered gluten-free and should be avoided.^2,7

Avoidance of dairy products

Some patients with untreated celiac disease may find that they are unable to tolerate dairy products when they are first diagnosed with the disease.¹²  The lactase enzyme, which is required to break down lactose in dairy products, is produced by cells that line the small intestine. In celiac disease, the production of the lactase enzyme is decreased due to the damage to the lining of the small intestine, resulting in lactose deficiency.²  Patients may choose lactose-reduced or lactose-free products if their symptoms are worsened by dairy products. Dairy products can be reintroduced after 3 to 6 months of a gluten-free diet when the lining of small intestine heals.

Dietary supplements

Patients with vitamin malabsorption may also receive a multivitamin preparation and appropriate supplements to correct nutritional deficiencies, including iron, folate, B vitamins, copper, and zinc. Other dietary supplements may include calcium and vitamin D for those individuals with hypocalcemia (low calcium) and osteopenic bone disease to prevent further bone loss.²

Gluten in medications

Inactive ingredients used as binders for medication pills or tablets may sometimes include starches or starch derivatives that contain gluten. In other cases, medications may come into contact with gluten during the manufacturing process. It is thus important for patients with celiac disease to be vigilant in checking the content of their medications with their pharmacist prior to taking them.¹¹ A helpful online resource is the website: http://www.glutenfreedrugs.com/, which is maintained by a clinical pharmacist and contains a list of medications that are gluten-free.¹²

Complications of celiac disease

It is important for patients with celiac disease to maintain a gluten-free diet for life to avoid complications of the disease.² Complications of celiac disease can include¹³:

§  Malnutrition

§  Nonresponsive celiac disease, where patients continue to experience symptoms despite a gluten-free diet, commonly due to unintentional ingestion of food contaminated with gluten.

§  Dermatitis herpetiformis, a skin condition where patient has very itchy bumps and blisters that look similar to those caused by the herpes virus. These bumps and blisters usually go away gradually after gluten is removed from the diet.

Where can I find more information?

§  Academy of Nutrition and Dietetics (formerly American Dietetic Association) (www.eatright.org)

§  American Celiac Disease Alliance (www.americanceliac.org)

§  American Gastroenterological Association (http://www.gastro.org/patient-center/digestive-conditions/celiac-disease)

§  Celiac Disease Foundation (www.celiac.org)

§  National Foundation for Celiac Awareness (NFCA) (www.celiaccentral.org)

§  National Library of Medicine (www.nlm.nih.gov/medlineplus/celiacdisease.html)

§  North American Society for the Study of Celiac Disease (www.nasscd.org)

References

1.     Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357(17):1731-1743.

2.     Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med. 2002;346(3):180-188.

3.     Czaja-bulsa G. Non coeliac gluten sensitivity - A new disease with gluten intolerance. [published ahead of print August 29, 2014]  Clin Nutr. pii: S0261-5614(14)00218-0. doi: 10.1016/j.clnu.2014.08.012.

4.     Binder HJ. Chapter 294. Disorders of Absorption. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid=331&Sectionid=40727087.  Accessed November 21, 2014.

5.     Tack GJ, Verbeek WH, Schreurs MW, Mulder CJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol. 2010;7(4):204-213.

6.     Schuppan D. Current concepts of celiac disease pathogenesis. Gastroenterology. 2000;119(1):234-242.

7.     Schuppan D, Dieterich W Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults.  In: Post TW, ed. UpToDate. Waltham, MA: UpToDate; 2014. www.uptodate.com. Accessed November 21, 2014.

8.     Chin RL, Sander HW, Brannagan TH, et al. Celiac neuropathy. Neurology. 2003;60(10):1581-1585.

9.     Pink IJ, Creamer B. Response to a gluten-free diet of patients with the coeliac syndrome. Lancet. 1967;1(7485):300-304.

10.  Celiac Disease Foundation. What Can I Eat? http://celiac.org/live-gluten-free/glutenfreediet/food-options/. Accessed December 12, 2014.

11.  King AR. Gluten Content of the Top 200 Medications: Follow-Up to the Influence of Gluten on a Patient's Medication Choices. Hosp Pharm. 2013;48(9):736-743.

12.  Gluten and Medications. http://www.glutenfreedrugs.com/. Accessed December 15, 2014.

13.  Kelly CP, Dennis M. Patient information: Celiac disease in adults (Beyond the Basics). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate; 2014. www.uptodate.com. Accessed December 12, 2014.

Prepared by:

Lim Yi Jing, RPh

PharmD Candidate, 2015

National University of Singapore

Headache Pain—Causes and Treatment with Nonprescription Analgesics

Headache disorders can be disabling, and they are one of the most common pain conditions affecting people worldwide. Globally, two-thirds or more of all adults will experience some form of headache disorder in their lifetime.¹ Despite the debilitating nature of headache disorders, they are rarely life-threatening, and most cases can be self-managed with nonprescription medications.

What are the different types of headaches in adults?

Headache disorders can be broadly classified into primary or secondary based on their cause. Primary headache disorders account for the majority and are not associated with an underlying illness. Tension-type headache is the most common form of primary headache, followed by migraine headache with or without aura. A small minority of patients have cluster headaches. Headaches caused by an underlying disease, such as infection, stroke, or head injury, are known as secondary headaches.² Anyone with characteristics of a secondary headache should consult a physician to evaluate whether the underlying cause is serious.

Tension-type headache

Tension-type headache often occurs when a person is experiencing stress, anxiety, or emotional conflicts; hence, it is also commonly referred to as a stress headache.² The pain is usually mild to moderate and is often described as a pressure or tightness affecting both sides of the head. Some people with tension-type headaches experience light sensitivity or sound sensitivity during the headache episode.³ The role of stress in tension-type headache is not clear, although some researchers believe that stress aggravates the abnormal pain processes already present in those individuals with headaches.⁴

Migraine headache

Migraine headache occurs less commonly than tension-type headache and is typically characterized by a throbbing pain that can affect either one or both sides of the head. In contrast to tension-type headache, migraine pain tends to be more severe and is often aggravated by day-to-day physical activities. Migraine headache can cause nausea or vomiting and may make you more sensitive to light and sound. Approximately 1 in 4 people with migraines develop an aura prior to the onset of the headache.⁵ The aura can be as short as 5 minutes or as long as 60 minutes.³ Symptoms of aura include blind spots (scotomas), seeing zig-zag patterns, feeling a prickling sensation on the skin, and difficulty in recalling or speaking intended words or phrases.⁶ The exact cause of migraine is still not clear, but changes in nerves and blood vessels in the brain may play a role.³

Cluster headache

Cluster headache is an uncommon type of primary headache characterized by an excruciating one-sided pain that typically begins in or around the eye or along the temple.  The attacks occur in clusters of weeks to months, separated by periods of no headache that can last for months to years.³ Treatment of cluster headache requires the use of prescription medications, and a physician consult is advised. Several links are provided at the end of this article if you would like to find out more about cluster headaches.

Medication-overuse headache

Medication-overuse headache is a form of secondary headache that results from taking pain-relieving medications too frequently. This type of headache occurs almost daily or every other day. Most people with medication-overuse headaches start off with a history of episodic headaches that triggers frequent use of pain-relieving medication. They subsequently develop a medication-overuse headache, which manifests as either a new type of headache or a marked worsening of their pre-existing headache disorder.³ Non-prescription medications that may cause this type of headache include acetaminophen, caffeine, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen.²

How are headache disorders evaluated and diagnosed by a physician?

In most cases, headache disorders are evaluated and diagnosed primarily on a thorough review of the headache history.⁷ Your physician or healthcare provider will ask you to describe, as completely as possible, the signs and symptoms experienced during the headache episode. Information that will help your provider in the evaluation of your headache disorder include the location of the pain, the type of pain, the frequency and duration of the headache episodes, and the presence of associated symptoms (such as nausea, nasal stuffiness, or light or sound sensitivity).

When should I seek medical attention for my headache symptoms?

Headaches are rarely symptoms of serious illness and most cases can be managed with non-prescription remedies. Occasionally, headache may be a sign of a more serious underlying medical condition (such as stroke, tumor, or infection) that will require prompt medical attention. Consult your physician if you experience any of the following “red flag” warning symptoms^7,8:

·       Headache that is sudden in onset or rapidly becomes severe should be treated as an emergency and you should seek medical attention immediately.

·       Headache that can be described as the “worst headache of your life”

·       Headache precipitated or worsened by exertion (e.g., coughing, sneezing, bending over)

·       A new onset of headache after age of 50 years

·       Headache accompanied by neck stiffness, fever, or confusion

·       Headache associated with trouble seeing, weakness, or numbness 

·       Headache that progressively worsens over weeks to months

In addition, if you have frequent headaches that require more than 2 to 3 doses per week of non-prescription pain-relieving medication, it is recommended to seek medical advice. This is because taking pain-relieving medications too often can potentially cause medication-overuse headache later. Your physician may prescribe a preventive therapy to help to reduce the frequency and severity of the headache.

What non-medication therapies can I use to self-manage my headache?

A lifestyle with a healthy diet, regular exercise and sleeping patterns, avoidance of excess caffeine and alcohol, smoking cessation, and stress reduction is beneficial for most patients with headaches.⁸ A headache diary may also be helpful. Write down when your headaches start, what you were doing at the time, how long the headaches lasted, and if anything provides relief. Keeping a headache diary can help to identify triggers and monitor the frequency, severity, and response of your headache to treatment.⁸ Irregular sleep patterns, stress, menstruation, skipping meals, or taking certain foods such as chocolate and alcohol have been identified as some of the triggers that precipitate migraine attacks.² Triggers differ from person to person; once you identify your triggers, you can modify these risk factors to reduce the frequency of your migraine attacks.

What are non-prescription medications that I can use to treat headaches?

Available non-prescription analgesics for the management of headache include acetaminophen and NSAIDs. Tension-type headaches tend to be mild and can be treated successfully with non-prescription medications in most cases. Non-prescription analgesics also have a role in the treatment of acute migraine attack for some people. Medications such as aspirin, ibuprofen, naproxen, or the combination of acetaminophen-aspirin-caffeine have been recommended as a first-line treatment for mild-to-moderate migraine attacks.⁹ Acetaminophen alone has also been found to be effective for treatment of mild-to-moderate migraine attacks.¹⁰ Regardless of the medication used, you should take an appropriate dose of pain-relieving medication early in the course of headache. It is also important to keep in mind that frequent use of non-prescription pain-relieving medications is not appropriate and indicate the need to consult a physician for evaluation of the headache.

Acetaminophen

Acetaminophen is effective in relieving mild to moderate pain. It has few side effects when taken as recommended. However, severe liver damage has been reported with the use of acetaminophen, particularly among people taking more than 4,000 mg in a day.¹¹ These people often took more than one drug containing acetaminophen. Because there are so many non-prescription and prescription products containing acetaminophen, it is important to be aware of which products contain acetaminophen to avoid accidental overdose. However, some people may be at higher risk of the adverse liver side effect of acetaminophen, even at the usual recommended doses. If you are unsure of what dose of acetaminophen to take, which products contain acetaminophen, or whether acetaminophen is safe for you, consult your pharmacist for advice.

 

Non-steroidal Anti-inflammatory Drugs

NSAIDs are a group of medications that are effective for relieving pain and reducing fever and inflammation. Several NSAIDs are available without a prescription, and these include aspirin, ibuprofen, and naproxen. NSAIDs are generally well-tolerated but side effects can occur. Common side effects that people report with NSAID use is stomach upset (dyspepsia) and heartburn. Taking NSAIDs with food, milk, or an antacid may help to reduce these gastric side effects.² Severe stomach bleeding is uncommon, but has been reported in people taking NSAIDs. If you are 60 years or older, have a history of stomach ulcers or bleeding problems, are taking a blood thinner or steroid medications, or are taking NSAIDs for a longer period of  time than recommended, you may be at a higher risk of severe stomach bleeding.¹² Consult your pharmacist to find out more about the dose, proper use, potential side effects, and drug interactions for NSAIDs before starting the medication.

Where can I find more information?

·       National Headache Foundation

-        http://www.headaches.org/content/my-headache

·       Cleveland Clinic – Diseases & conditions resources     https://my.clevelandclinic.org/health/diseases_conditions/hic_Overview_of_Headaches_in_Adults

·       American Headache Society

-        http://www.americanheadachesociety.org/professional_resources/headache_fact_sheets/

·       Headache Journal Patient Education Page

-        http://www.headachejournal.org/view/0/toolboxes.html

 

References

1.     Stovner Lj, Hagen K, Jensen R, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193-210.

2.     Wilkinson JJ. Headache. In: Krinsky DL, Berardi RR, Ferreri SP, Hume AL, Newton GD, Rollins CJ, Tietze KJ eds. Handbook of Nonprescription drugs: An Interactive Approach to Self-Care. 17^th ed. Washington, DC: American Pharmacists Association; 2012: 67-86.

3.     Headache classification committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013; 33(9): 629-808.

4.     Cathcart S, Winefield AH, Lushington K, Rolan P. Stress and tension-type headache mechanisms. Cephalalgia. 2010;30(10):1250-1267.

5.     Cutrer FM, Bajwa ZH, Sabahat A. Pathophysiology, clinical manifestations, and diagnosis of migraine in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed on November 23, 2014.

6.     Evans, RW. The clinical features of migraine with and without aura. Cataracts and refractive surgery today. March 2014: 51-60. http://bmctoday.net/crstoday/pdfs/crst0314_mf2_evans.pdf. Accessed November 23, 2014.

7.     Hainer BL, Matheson EM. Approach to acute headache in adults. Am Fam Physician. 2013;87(10):682-687.

8.     Beithon J, Gallenberg M, Johnson K et al. Institute for Clinical Systems Improvement. Diagnosis and Treatment of Headache. 11^th edition. http://bit.ly/Headache0113. Updated January 2013. Accessed November 23, 2014.

9.     Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55(6):754-762.

10.  Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M. Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study. Arch Intern Med. 2000;160(22):3486-3492.

11.  Acetaminophen (paracetamol): patient drug information. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed on December 12, 2014.

12.  Food and Drug Administration. Organ-specific warnings; Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; final monograph. http://www.gpo.gov/fdsys/pkg/FR-2009-04-29/pdf/E9-9684.pdf. Published April 29, 2009. Accessed November 23, 2014.

Prepared by:

Christina Tan, RPh

PharmD Candidate

National University of Singapore