Nutrition and oral mucosal diseases

Clinics in Dermatology (2010) 28, 426–431

Nutrition and oral mucosal diseases Danielle Marie Thomas, BAa , Ginat W. Mirowski, DMD, MDb,⁎ a

Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA Department of Oral Pathology, Medicine, and Radiology, Indiana University School of Dentistry, 1121 W Michigan St, Indianapolis, IN 46202, USA b

Abstract Oral manifestations of nutritional deficiencies can affect the mucous membranes, teeth, periodontal tissue, salivary glands, and perioral skin. This contribution reviews how the water-soluble vitamins (B2, B3, B6, B12, C, and folic acid), fat-soluble vitamins (A, D, and E), and minerals (calcium, fluoride, iron, and zinc) can affect the oral mucosa. © 2010 Elsevier Inc. All rights reserved.

Introduction The oral manifestations of nutritional deficiencies include nonspecific signs and symptoms that involve the mucous membranes (wet tissues of the oral cavity), the teeth and the periodontal tissues (bones and gingiva surrounding and supporting the teeth), the salivary glands, and the perioral skin. Vitamins and minerals are valuable in maintaining healthy mucous membranes. Nutritional deficiencies are related to the abnormal intake of vitamins and minerals. Owing to the rapid rate of cell turnover in the mucous membranes (3 to 7 days)1 compared with the skin (up to 28 days),2 the oral cavity may exhibit early signs and symptoms of systemic disease or nutritional deficiencies. Activities such as eating, drinking, and breathing affect mucous membranes that are weakened by deficiencies. In addition, the local microenvironment of the mouth is nonsterile; thus, commensal and pathologic microorganisms may further stress the weakened mucous membranes.1 Not all vitamins and minerals affect the oral mucosa. Water-soluble vitamins that have oral mucosal involvement

⁎ Corresponding author. Tel.: +1 317 274 5141; fax: +1 317 566 0878. E-mail address: [email protected] (G.W. Mirowski). 0738-081X/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2010.03.025

include vitamins B2, B3, B6, B12, folic acid, and vitamin C. Water-soluble vitamins are not stored in the body in large amounts, so they must be supplied to the body by the diet on a frequent or daily basis.1 Fat-soluble vitamins that affect the mucosa include vitamins A, D, and E. Minerals relevant to the oral mucosa are calcium, fluoride, iron, and zinc.

Water-soluble vitamins Vitamin B1 (thiamine) assists with metabolic reactions, such as converting carbohydrates to fat, and converting amino acids, carbohydrates, and fats to energy. At high risk for vitamin B1 deficiency are alcoholics, chronically ill patients undergoing parenteral feeding, women with prolonged hyperemesis gravidarum, and anorexics.1,3 The two main conditions caused by thiamine deficiency, beriberi and WernickeKorsakoff syndrome,1 do not have oral manifestations. Vitamin B2 (riboflavin), in its metabolically active form, is part of the flavin mononucleotide and flavin adenine dinucleotide coenzymes, which aid enzymes in several intermediary metabolism reactions.4 Patients who have malabsorption are at risk for developing edema of the pharyngeal and oral mucous membranes, angular cheilitis, stomatitis, and glossitis.1,3

Nutrition and oral mucosal diseases Vitamin B3 (niacin) is involved with cell repair, and its coenzymes serve in a variety of reactions, including tissue respiration and glycolysis. At high risk of vitamin B3 deficiency are alcoholics and patients with congenital defects of the intestines and kidneys that prevent effective tryptophan absorption.1,5 Deficiency, referred to as pellagra, manifests as bright red glossitis, burning mouth, erythema of the gingiva, and dental carries.1,3 Vitamin B6 (pyridoxine) is involved in carbohydrate, fat, and protein metabolism, as well as other key reactions such as converting tryptophan to niacin, heme biosynthesis, and neurotransmitter synthesis.1 Vitamin B6 also assists in clearing blood of homocysteine.1 At high risk are alcoholics and patients taking medications that react with B6 such as isoniazid, L-dopa, penicillamine, and cycloserine.1 Deficiency presents orally as glossitis, cheilitis, and erythema of the gingiva.1,3 Vitamin B9 (folic acid) aids in DNA synthesis and is critical to cells with a rapid turnover rate that require continual DNA creation. Folic acid also is involved in forming the blood cells in the bone marrow. It is associated with vitamin B12, and hematologic changes occur if either one is deficient. At high risk for deficiency are the elderly, alcoholics, and those taking medications that interfere with it, such as methotrexate and phenytoin. Deficiency leads to megaloblastic anemia. Clinical manifestations include burning of the tongue and oral mucosa, a red and swollen tongue, and angular cheilitis.1 Vitamin B12 (cobalamin) is also required for DNA synthesis. The elderly, vegetarians, and those with resected stomach or ileum are particularly susceptible to deficiency of this vitamin. Deficiency of vitamin B12, pernicious anemia, presents with megaloblastic anemia, and manifests orally as a red, atrophic, beefy, burning tongue.1,3 In addition, vitamin B12 deficiency, along with folic acid and iron deficiencies, is associated with recurrent aphthous stomatitis. Deficiencies of these nutrients were found in 18% to 28% of individuals with recurrent aphthous stomatitis, which improves in some patients once the deficiency is eliminated.6 Vitamin C (ascorbic acid) is a powerful antioxidant that is a cofactor in hydroxyproline formation, which is necessary for healthy collagen formation,7 and it also enhances iron absorption.1,5 At high risk of vitamin C deficiency, scurvy, are alcoholics and individuals who consume no fruits or vegetables, elderly people, and infants who consume only cow's milk.1,5 Smokers, in particular, who are deficient in vitamin C face the highest likelihood of developing periodontal disease.9 Scurvy presents with hemorrhagic gingivitis with enlarged blue or red gingiva, gingival bleeding, swollen gingiva, and infections.1,7 Scurvy also affects dentition, presenting with loose teeth, interdental infarcts, and tooth loss.1,10 The likelihood of periodontal disease has been shown to be 20% greater with low intakes of vitamin C.9

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Fat-soluble vitamins Fat-soluble vitamin A is also critical to maintaining oral health. Vitamin A is responsible for photosensitive pigments such as rhodopsin, maintaining epithelial tissue, and preventing infectious diseases. Vitamin A also provides for the growth and modeling of bones and teeth.1,11 At high risk for deficiency are patients with malabsorption and fatabsorption disorders, such as celiac sprue and short-bowel syndrome.1,5 The oral manifestations of vitamin A deficiency include xerostomia (dry mouth), reduced resistance to infections, and impaired growth of the teeth. Because vitamin A is fat soluble, it can be stored in the body tissues at toxic levels. The oral manifestations of toxicity include cheilitis, gingivitis, carotenemia (orange discoloration of the mucous membranes due to excessive deposition of pigment), and impaired healing.12 At risk for vitamin A toxicity are patients whose livers are compromised due to drug abuse, hepatitis, or excessive ingestion of carrots.1 Through its role as the facilitator of calcium absorption from the intestines and the removal or deposit of calcium from the bones, vitamin D is responsible for maintaining serum homeostasis of calcium.1 At high risk for calcium deficiency are the elderly, women who have had multiple pregnancies, and low-birthweight infants.1,12 Although vitamin D deficiency may increase the likelihood of the loss of periodontal attachment,7 it lacks other mucosal findings. Vitamin E (tocopherol) is an antioxidant whose deficiency may be associated with oral cancer. At high risk for vitamin E deficiency are premature infants and patients with malabsorption disorders or lipid transport abnormalities.1

Minerals Calcium is a major component of teeth and bones. At high risk for calcium deficiency are premature infants who do not go through the critical intrauterine phase where 80% of the body's calcium, phosphorus,, and magnesium are absorbed and who also may have malfunctioning kidneys that fail to metabolize vitamin D adequately.12 Low calcium intake is associated with an increased risk of periodontal disease.10 Conversely, increased calcium intake has been shown to be associated with decreased risk of periodontal disease and tooth loss, in part due to its role in preventing systemic bone loss.11 Fluoride makes tooth enamel less soluble and more resistant to demineralization.1 Although fluoride deficiency does not affect the mucous membranes, it is associated with an increased incidence of dental caries. Toxicity, however, causes mottling of the enamel, ranging from mild white flecks to extreme brown discoloration and enamel pitting.1 Iron is important in many different aspects of normal function. As a component of hemoglobin, iron is critical for

428 oxygen transport. Iron is essential for adenosine triphosphate production and normal immune function and is a cofactor with vitamin C in collagen production.1,12 Pregnant women and patients with unusual blood loss or malabsorption disorders are at elevated risk for iron deficiency. Consumption of phytates, oxalates, coffee, and tea reduce iron absorption, whereas vitamin C enhances it.1 Iron deficiency is the most common deficiency in the United States of America.12 Oral manifestations of irondeficiency anemia include atrophy of the lingual papillae, burning and redness of the tongue, angular stomatitis, dysphagia, and pallor of the oral tissues due to underlying anemia.1,12 Iron deficiency has been shown to predispose rats to caries, while an iron-supplemented diet has shown a reduction in caries.12 Like folic acid and B12, iron deficiency may be associated with recurrent aphthous ulcers.6 Although the cause of Plummer-Vinson syndrome is still uncertain, this syndrome is associated with iron deficiency, along with genetic factors, and presents with angular stomatitis, glossitis, and dysphagia.3 Zinc plays a variety of critical roles in the cell, particularly acting as an enzymatic cofactor critical for cell growth and reproduction, normal immune function, metabolism, and as a stabilizer of DNA and RNA and collagen synthesis.1 At high risk for deficiency are pregnant women, the elderly, vegans, alcoholics, diabetics, and those with HIV/AIDS, inflammatory bowel disease, and sickle cell disease.5 Excessive consumption of calcium, iron, copper, fiber, phytates, and phosphate salts interferes with proper zinc absorption.1 Oral manifestations of zinc deficiency include changes to the epithelium of the tongue, an increase in cell numbers, and flattened filiform papillae, ulcers, and xerostomia. 1,12 Impaired wound healing is one of the most damaging effects of deficiency.5,11,12 Zinc enhances taste and appetite, so deficiency also results in decreased taste sensation, which can cyclically contribute to the malnutrition problem.11,12 Finally, acrodermatitis enteropathica is a fatal metabolic disorder that hinders the uptake of zinc. Oral mucous membranes may be secondarily infected with Candida or Staphylococcus.

The role of diet in disease of the mucous membranes Certain populations are particularly predisposed to vitamin and mineral deficiencies, whether due to diseases that affect absorption, lifestyle behaviors, or diet quality. Individuals with eating disorders, such as anorexia nervosa and bulimia, are susceptible to numerous deficiencies that may affect the mucous membranes, the teeth, periodontal tissues, salivary glands, and perioral tissues.13 Associated psychologic conditions, including major depression or dysthymia, anxiety disorders, obsessive-compulsive disorders, and alcohol or substance abuse, can compound local

D.M. Thomas, G.W. Mirowski effects on the oral cavity and include poor dental care, abuse of medications, and altered nutritional habits. Anorexic patients obsessively decrease their body weight by determined dieting and compulsive exercise. In contrast, bulimic patients control their weight by purging with or without binge eating. This is accomplished by self-induced vomiting after eating. The amount of food ingested may be normal or massive. Patients in both groups suffer from disturbed body image and a variety of other fears. Although eating disorders occur predominantly in women, 5% to 15% of anorexics and bulimics are men. Anorexia nervosa accounts for 65%, while 35% of patients have bulimia. The lifetime risk for women is 0.3% to 1%.14 Anorexia tends to develop during the adolescent years, whereas bulimia develops during the late teen years and early 20s. Mucosal atrophy and glossitis (erythema and atrophy of the tongue) are predominantly caused by vitamin deficiencies. Erythematous patches and erosion on the soft palate may be due to trauma induced when purging is initiated. Occasionally, scarring on the dorsal aspect of the fingers or hands due to repeated trauma of the finger initiated by the self-induced purging is observed. Dental erosion (loss of enamel surface) may be caused by ingestion of carbonated drinks. Severe erosion of enamel due to acids from frequent vomiting presents with classic lingual erosion of the maxillary anterior teeth (Figure 1). Salivary glands may be enlarged (“chubby cheeks”) and show sialadenosis or necrotizing sialometaplasia on biopsy. Burning mouth may be due to mucosal atrophy, nutritional deficiencies, candidiasis, or drug abuse. Tooth pain or dental sensitivity may be due erosion or decay.15 No diagnostic serologic tests are available to confirm the diagnosis of an eating disorder. Thus, the diagnosis is based on history, recognizing subtle and nonspecific clinical signs, and a psychologic evaluation. Treatment of eating disorders is very complex and requires a multidisciplinary approach, including medical and psychiatric care as well as nutritional guidance. Prompt weight restoration is necessary and may be difficult to initiate in the outpatient setting. Vegetarians and vegans are at high risk for vitamin B12 deficiency, because the primary food sources of B12 are animal based.16 This group should pay particular attention to obtaining recommended B12 levels through other sources, such as a multivitamin. The prevalence of caries is lower in vegetarians relative to nonvegetarians, possibly because they consume primarily plant-based diets, which are more fibrous than meat-based diets.17 Users of tobacco and illicit drugs are at high risk for nutritional deficiency and its manifestations in the oral mucosa due to associated lifestyle habits and to the affect of the substances on the mucosa. Tobacco use is associated with alcohol consumption and poor diet, which increase the risk for deficiency.18 Smoking is also a strong risk factor for periodontal disease.10

Nutrition and oral mucosal diseases

Fig. 1 Lingual erosion of maxillary anterior teeth in a patient with recurrent vomiting.

Illicit drug use is associated with poor personal hygiene, homelessness, and erratic eating habits.19 In particular, methamphetamine (meth) users in California and Midwestern states tend to be young individuals with poor dietary and hygiene habits, such as not brushing teeth, eating snacks without eating defined meals, and consuming carbonated drinks.20 Meth use leads to a periodontal presentation called “meth mouth,” which is identified by advanced tooth decay and xerostomia (Figure 2).21 Meth users also have more visible plaque and fewer molars than the general population.20 Similar to meth users, hashish users have a high caries tendency, which is likely linked to the craving for sweets associated with hashish consumption.22 Alcoholics are another group at high risk for nutritional deficiencies and who present with particular patterns of oral manifestation. Alcoholic hepatitis is commonly accompanied by malnutrition, anemia, and vitamin deficiencies. These patients present with pallor, angular cheilitis, and glossitis.12 Untreated alcoholic hepatitis can progress to liver cirrhosis, which is identified by the yellow tint of the mucous membranes (particularly along the ventral surface of the tongue), yellow sclera, and cutaneous jaundice.12 Alcoholics are particularly susceptible to developing thiamine deficiency because alcohol interferes with the absorption of thiamine.5 Finally, caries also tend to be extensive amongst alcoholics because of decreased salivary flow and the clustered lifestyle behaviors tending to neglected oral hygiene.12 Patients with diabetes are at greater risk for developing oral infections and periodontal disease than nondiabetic patients.12 Diabetics may experience oral candidiosis and periodontitis as a result of their immunocompromised condition, delayed wound healing, and reduction of saliva due to xerostomia.11,22-24 Burning tongue, altered taste, and dysesthesias are also common oral symptoms.13,24 Due to these concerns, it is recommended that diabetics pursue a diet low in cariogenicity and consume meals containing specific nutrients at regular intervals.12

429 The elderly are another group at great risk for nutritional deficiency. Obesity and under-nutrition are the most common nutritional disorders for people aged older than 65. Dentures have a bidirectional effect on nutrition and oral health: they are often the result of poor oral health and in turn reduce nutritional and oral health status. Twenty-six percent of adults aged 65 to 69 have no natural teeth.25 Dentures may cause biting and chewing problems. The chewing function of a patient with complete dentures is only 20% that of a dentate person.26 Dentures also limit food selection, making the patient inclined to consume smooth soft foods that are easier to eat but often less nutritious. Edentulous patients have less nutritional diets than dentate people.25 Nutrient intake is correlated with the number of posterior occluding pairs of natural teeth a person has.27 For example, intake of vitamin A, fiber, and calcium declines as number of teeth decline.26 Edentulous adults were found to have lower levels of retinol, β-carotene, ascorbate, tocopherol, and folic acid than dentate adults.11 Adults with dentures may also experience embarrassment about eating in public, reduced appetite, and reduced pleasure in eating, which further compromises their nutritional status. Prescription drug use may alter nutritional health by affecting absorption, metabolism, and excretion.28 Polypharmacy and its resulting xerostomia is particularly a challenge for elderly patients. The average 75-year-old individual has three chronic conditions and uses five different prescription drugs.29 Xerostomia is a side effect of numerous medications, including antihistamines, antihypertensives, antidepressants, and antipsychotics.1 Xerostomia is associated with increased risk of oral candidiosis, caries, and periodontal disease. It also affects taste and texture perceptions, makes dentures less comfortable to wear, and increases the difficulty of eating.25 Patients with xerostomia experience deficient potassium, vitamin B6, iron, calcium, and zinc intakes.11 Other drug affects on oral health include gingival hyperplasia, a common side effect of

Fig. 2 Caries in a patient with a history of methamphetamine habit (photo courtesy of Vikas Puri, IUSD).

430 phenytoin therapy, due to its interference with vitamin D metabolism.28 Gingival hyperplasia is also a side effect of calcium channel blockers and cyclosporine A.3,28 Finally, the elderly are susceptible to vitamin D deficiency due to reduced exposure to sunlight and reduced efficiency of vitamin D synthesis through the skin.25 HIV patients may experience painful burning sensations, dysphagia, and a susceptibility to oral viral diseases such as herpes simplex and cytomegalovirus infections that lead to chronic ulcerations or hairy leukoplakia.24 The pain caused by oral infections commonly found in AIDS patients can reduce the appetite and increase the difficulty of eating, further leading to a poor diet.12 Studies have also suggested that HIV-positive patients require higher vitamin C levels than the recommended daily allowance.30 HIV-positive patients should follow a nutrition plan that focuses on eating small, frequent meals that are high in calories and nutrients.12 Gastrointestinal disease, Crohn disease, cystic fibrosis, obstruction of the bile ducts, and malabsorption result in deficiencies of the fat-soluble vitamins A, D, E, and K and in general malnutrition. Ulcerative colitis results in the potential malabsorption of vitamin K, vitamin B12, and folic acid.31 Patients may experience delayed healing, increased risk of infection, pyostomatitis vegetans, and hairy leukoplakia.31,32 Treatment involves determination of the patient's liver function and attention to avoiding toxic dosage of drugs because the patient may have a reduced metabolism. Before completing any surgery, the patient should be evaluated for anemia and bleeding disorders due to vitamin K deficiency.31 Crohn disease leads to impaired absorption of nutrients, particularly calcium, iron, folic acid, vitamin B12, and fatsoluble vitamins. These deficiencies lead to pallor, angular cheilitis, and glossitis.31,33 Oral lesions are found in 6% to 20% of patients with Crohn disease.31 Patients experience pyostomatitis vegetans, orofacial granulomatosis, and inflammatory hyperplasias of oral mucosa with a cobblestone pattern.31,33 Patients with Crohn disease need to pay careful attention to their nutrition to avoid these deficiencies. In addition to other malabsorption diseases, atrophic gastritis leads to pernicious anemia, manifested orally as a beefy red tongue with the filiform papillae denuded, giving the tongue a bald appearance.32 Nomas are found in conditions of extreme poverty where the otherwise treatable ulcer progresses to become a painful and potentially deadly wound. These dangerous ulcers were common in Europe and North America until the early 20th century. Since then, they have no longer been common in developed nations, except for cases in concentration camps during World War II, patients with HIV, and Native American youths with severe combined immunodeficiency syndrome.34 They are still prevalent in developing nations, however, particularly in Africa,9 with the highest incidence occurring at 1 to 4 years of age.34 The distribution pattern of noma follows the distribution of malnutrition and vitamin A deficiency extremely closely in

D.M. Thomas, G.W. Mirowski children younger than 5.35 Nomas are most common in extremely impoverished communities where severe malnutrition is rampant along with conditions such as unsanitary drinking water, lack of access to health care, poor sanitation, and high infant mortality.34 Early symptoms of noma include bad breath, potent discharge, excessive salivation, cervical lymphadenopathy, high fever, anemia, high white-cell count, growth failure, and other manifestations of malnutrition.35 Swelling is the first externally visible sign, followed by a blackish pit where tissue is being lost, and finally, a well-marked perimeter around a blackish necrotic cluster. The sloughing of the necrotic soft tissue is quickly followed by sequestration of exposed bone and teeth.34 Nomas lead to severe disfigurement, functional loss, and ultimately, death. In its early stages, noma can be easily treated with antibiotics, local disinfection, and nutritional counseling.34,35 Acute noma requires antibiotics, antiseptic wound care, removal of tissue slough, and sequestra. In addition, the underlying malnutrition and dehydration as well as associated diseases such as malaria, measles, and HIV must be addressed.34

Conclusions The myriad of oral manifestations of various nutritional deficiencies affect the health of our patients. It is often difficult to definitively identify the deficiency without a complete history and physical evaluation. Mucosal changes, tooth findings, and evaluation of the signs and symptoms of the oral cavity may play a significant role in targeting the workup and treatment of these complex patients.

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