G.I. Disease

Oral Manifestations of Gastrointestinal Disease

A variety of gastrointestinal diseases can be associated with lesions of the oral cavity. The lesions usually correlate to active intestinal disease, but they may present prior to any other evidence of the disease and even be used to initiate diagnosis and treatment. This paper reviews the more common oral manifestations of gastrointestinal disease and their dental management.

It is not uncommon for a variety of systemic conditions to be associated with lesions of the oral cavity. This is particularly true of gastrointestinal diseases. The lesions usually correlate with active intestinal disease. On occasion, however, they may present prior to any evidence of gastrointestinal disease and initiate diagnosis and treatment of the underlying disease process. These lesions may cause severe discomfort to the patient. In some cases, they even cause extreme destruction to the teeth and periodontium, which results in premature loss of teeth. It is, therefore, important that the oral manifestations be recognized and managed appropriately.

This paper will review the more common oral manifestations of gastrointestinal diseases (Table 1) and the appropriate dental management.

Nutritional Deficiencies

Anorexia Nervosa and Bulimia

Figure 1. Bulimia — severe palatal and occlusal erosion of the maxillary teeth causing the incisal edges of the incisors to be thin and knife-edged. The occlusal surfaces have a flat to cupped-out appearance.

Anorexia nervosa and bulimia are psychological disorders that are generally seen in young to middle-aged females. These patients perceive themselves as fat and become obsessed with losing weight. Patients with anorexia nervosa often appear emaciated. They may stop eating or gorge themselves secretly and subsequently induce vomiting. Patients with bulimia tend to appear of normal weight and eat normally but engage in chronic self-induced vomiting. Both groups show oral signs of chronic regurgitation. There are varying degrees of chemical erosion of enamel and dentin, which is particularly noticeable on the palatal and occlusal surfaces of the maxillary teeth (Figure 1). The lower teeth are less severely affected, probably due to the protection of the tongue during vomiting. These patients also show increased susceptibility to caries and gingivitis, although plaque accumulation is not a prominent feature. Restorations often fail as the erosion progresses and the teeth become sensitive to hot and cold. Xerostomia, which is sometimes painful, is also common. These patients often deny the problem, but anorexia nervosa or bulimia should be considered when these characteristic oral changes are present. Patients should be advised to immediately rinse the mouth with water, a fluoridated mouthrinse, or antacids after vomiting. They should not brush the teeth immediately after vomiting as this may increase the erosive process. Daily self-application of fluoride in custom trays is also helpful. In addition, these patients may be subject to nutritional deficiencies and may manifest oral lesions associated with those deficiencies.

Iron-Deficiency Anemia

Iron-deficiency is the most common cause of anemia, and it typically affects young women of childbearing age. The iron deficiency is caused by chronic iron loss associated with excessive blood loss during menstruation. However, 2 percent of adult men are iron-deficient because of chronic blood loss associated with gastrointestinal disease. Peptic ulcer disease, diverticulosis, hiatal hernia, and colon cancer are the most likely underlying problems.

Oral manifestations include angular cheilitis, glossitis, and generalized mucosal atrophy, which may lead to ulceration. The dorsal surface of the tongue shows patchy or diffuse atrophy of the filiform papillae, and about 30 percent of patients will complain of soreness of the tongue or mouth.¹ The gingiva, soft palate, and tongue may be pale. Oral candidiasis is sometimes present.

Diagnosis is made by appropriate laboratory testing. Iron-deficiency anemia is characterized by microcytic, hypochromic red blood cells, decreased hemoglobin, decreased serum iron, and increased total iron-binding capacity. It is important that the cause of the deficiency be identified, especially in adult men and postmenopausal women. Treatment consists of dietary iron supplementation and antifungal agents when appropriate.

A severe form of iron-deficiency anemia associated with glossitis and dysphagia is known as Plummer-Vinson syndrome. On examination of the esophagus, postcricoid webs are present. The fingernails also have a spoon-shaped morphology (koilonychia). Oral changes include those described above, although they may be more severe. Patients often are unable to tolerate dentures.

This condition has special significance in that it has been associated with a high frequency of oral squamous cell carcinoma. Therefore, in addition to correcting the underlying iron deficiency, clinicians should thoroughly evaluate these patients on a periodic basis for oral, pharyngeal, and esophageal cancer. Any suspicious lesions should be biopsied.

Pernicious Anemia

Pernicious anemia most often affects elderly patients of northern European descent and is caused by lack of intrinsic factor, which is produced by the parietal cells of the stomach. These cells also produce gastric hydrochloric acid. Parietal cells are probably destroyed by an autoimmune mechanism. Because intrinsic factor is necessary for the absorption of vitamin B-12 in the distal portion of the ileum, patients with pernicious anemia suffer from a vitamin B-12 deficiency even though their diet may be adequate. A similar condition has been reported following gastrointestinal bypass operations for weight control.²

Figure 2. Pernicious anemia — patchy area of mucosal erythema (courtesy of Dr. Sadru Kabani). Figure 3. Pernicious anemia — Areas of papillary atrophy, erythema, and ulceration on the dorsal tongue (courtesy of Dr. Sadru Kabani).

Oral manifestations include generalized atrophy of the oral mucosa leading to ulceration and focal patchy areas of oral mucosal erythema (Figure 2). Many patients complain of a burning sensation of the tongue, lips, and buccal mucosae. Aphthous ulcers have also been reported. Fifty to 60 percent of patients have tongue changes including erythema and atrophy³ (Figure 3). The tongue may also appear flabby because of loss of muscle tone.

Laboratory testing will reveal a macrocytic anemia and decreased levels of serum cobalamin (vitamin B-12). Treatment consists of monthly intramuscular injections of cyanocobalamin. The oral lesions respond rapidly, sometimes within five days. If not treated, pernicious anemia can lead to irreversible central nervous system damage because vitamin B-12 is necessary for myelin synthesis. Without vitamin B-12, demyelinization of the spinal cord will slowly occur over a period of years. The patients may experience ataxia, decreased vibratory sensation, and dysfunction of the urinary bladder.

Scurvy

Caused by a lack of vitamin C, scurvy is an uncommon disease in the United States. It is typically seen in young children whose diets often consist entirely of milk and in elderly edentulous men whose diet lacks fresh fruits and vegetables. Because of inadequate collagen synthesis, the vascular walls are quite weak and subject to injury. The oral manifestations include generalized gingival swelling with spontaneous hemorrhage. There may be rapid loss of supporting alveolar bone with loosening and loss of teeth. There is impaired wound-healing and an increased susceptibility to secondary infection.

Although this condition may appear clinically to represent a platelet problem, the platelet count and bleeding time values will be normal. The underlying vitamin C deficiency must be treated, or scurvy can lead to death.

Inflammatory Bowel Diseases

Crohn's Disease

Figure 4. Crohn's disease — portion of small intestine showing multifocal areas of thickening of the wall and narrowing of the lumen. Figure 5. Crohn's disease — giant cells and epithelioid macrophages in granulomatous inflammation. Figure 6. Crohn's disease — deep crateriform ulcer with rolled border and necrotic center as well as angular cheilitis. Figure 7. Crohn's disease — mucosal hyperplasia and fissuring with linear ulceration (courtesy of Dr. Mark Kernstein). Figure 8. Crohn's disease — mucosal edema, aphthaform ulcers and military granulomas (Courtesy of Dr. Mark Bernstein).

Crohn's disease is an inflammatory condition of unknown etiology that primarily affects the distal portion of the small intestine, rectum, and proximal colon. It may, however, affect the entire gastrointestinal tract, including the oral cavity. The affected areas of the intestine show fissuring, fistulae, and thickening (Figure 4), which often results in narrowing of the intestinal lumen. There are often several noncontiguous areas involved. Histologically, the intestinal lesions often show granulomatous inflammation (Figure 5). Extraintestinal symptoms may involve joints, skin, and eyes and are more common in patients with colonic involvement. Clinically, the gastrointestinal signs and symptoms include abdominal cramping, pain, nausea, and diarrhea.

The oral lesions are well-documented and typically involve the lips, gingiva, vestibules, and buccal mucosa. Less frequently, the tongue, palate, and pharynx may be involved. The lips often show edema, deep ulceration, and angular cheilitis (Figure 6). The gingiva often appears edematous and erythematous. A pattern of hyperplasia and fissuring (cobblestone appearance) may be seen. Deep linear ulcers are associated with the hyperplasia in the vestibular, buccal, and labial mucosa (Figure 7). Polypoid or papillary lesions are common in the vestibules, on the buccal mucosa, and on retromolar pad areas. Swelling and edema of the buccal mucosa and lips may lead to facial asymmetry. Occasionally, aphthaform ulceration has been reported (Figure 8). Additional lesions associated with Crohn's disease include metallic dysgeusia, erythema migrans, Melkersson-Rosenthal syndrome, and involvement of mandibular lymph nodes and salivary glands.

Oral lesions generally occur in the first three decades of life with 39 percent occurring to people younger than 16. In more than half the patients, the oral lesions recur. Histologically, the oral lesions have been reported to show noncaseating granulomas in 10 percent to 68 percent of cases.^4,5 Some studies have shown that oral manifestations may precede intestinal symptoms in 37 percent to 60 percent of patients.^5,6 This is of significance to the dental practitioner as patients may present first to the dental office because of the oral lesions.

It has also been recommended that in any patient with orofacial granulomatosis or in patients with chronic or relapsing but undiagnosed oral lesions, a complete gastrointestinal evaluation by esophagogastroduodenoscopy, ileocolonoscopy, and small bowel radiography be performed, even in the absence of gastrointestinal symptoms. It is further recommended that if the results are negative, the potential diagnosis of Crohn's disease should not be ruled out, and evaluation should be repeated at a later date. ⁵

Treatment of Crohn's disease generally includes systemic drug treatment with sulfasalazine or steroids and/or azathioprine as well as diet restriction. In severe cases, the complications of Crohn's disease such as fistulae and abscesses may necessitate surgical intervention. If a substantial portion of the distal ileum is removed or is severely involved by the disease, the patient may develop a vitamin B-12 deficiency anemia or vitamin K deficiency. Supplemental intramuscular injections of cyanocobalamin may be necessary. The possibility of vitamin K deficiency-associated coagulopathies should be considered and prothrombin time should be evaluated before invasive dental procedures are performed. These patients might also develop an iron-deficiency anemia because of malabsorption, limited diet, or the inhibitory effect of sulfasalazine on absorption of ingested folate. In these patients, oral manifestations of the nutritional deficiencies might also be present (see above descriptions).

Treatment of the oral lesions often consists of systemic and/or topical steroids in the forms of rinses, pastes, and ointments. The results have been variable in patients with orofacial granulomatosis. Approximately one-half of patients respond favorably with complete remission.⁵ The other half do not fare well and suffer multiple exacerbations. Plauth and colleagues recommend the use of systemic steroids and/or azathioprine if topical therapy fails to control symptoms.⁵ It should be kept in mind that the use of steroids may predispose the patient to the development of secondary infection with Candida. Treatment with antifungal agents may be necessary. In some cases, it may be necessary to alternate the use of different antifungal agents to avoid the development of resistant strains.¹

Ulcerative Colitis

Ulcerative colitis is an inflammatory condition of the bowel that primarily involves the colon and rectum. The gastrointestinal lesions consist of contiguous broad areas of hemorrhagic ulceration and small abscesses. Lesions are superficial and limited to the mucosa and submucosa. They do not extend into the muscularis. Clinical manifestations include bloody diarrhea; weight loss; generalized fatigue; and, often, fever.

Oral lesions of ulcerative colitis include recurrent major or minor aphthous ulcers, ulcers similar to pyoderma gangrenosum of the skin, and hemorrhagic ulcers of the oral mucosa. Aphthous ulcers are common, affecting 4 percent to 20 percent of patients.⁴ Their onset is usually sudden and, in many cases, coincides with exacerbations of the gastrointestinal symptoms.¹ The lesions of pyoderma gangrenosum are characterized by progressive necrosis with deep ulceration. These have been noted on the tongue in some patients.

Figure 9a. Ulcerative colitis — a segment of colon showing superficial, hemorrhagic mucosal and submucosal ulceration. Figure 9b. Ulcerative colitis — similar appearing ulcers of the buccal mucosa (courtesy of University of Oklahoma School of Dentistry).

The hemorrhagic ulcers seen in the mouth are quite similar to the lesions in the colon (Figures 9a and 9b). They are irregular in shape, superficial, and of varying size. Similar lesions are also seen on the skin of the cheeks, inner aspects of the thigh, buttocks, and lower abdomen. The lesions may start as a hemorrhagic blister and over one to three days burst and progress to ulceration.

Treatment of ulcerative colitis involves the use of sulfasalazine and /or systemic steroids. In severe cases, surgical resection may be necessary. Patients with ulcerative colitis also seem to have an increased risk of the development of colon cancer. Periodic thorough evaluation is essential for early detection. In addition, approximately 7 percent of patients have some liver abnormality ranging from abnormal laboratory values to sclerosing cholangitis and postnecrotic cirrhosis.⁷ Therefore, regular monitoring of liver function is also recommended.

Oral complications of the medical management of ulcerative colitis are similar to those seen in Crohn's disease and include possible nutritional deficiencies and anemia, particularly iron-deficiency anemia. Iron deficiency may be due to chronic blood loss from the gastrointestinal lesions as well as malabsorption, limited diet, and the inhibitory effect of sulfasalazine on absorption of ingested folate. Secondary candidal infections are also common.

Successful treatment of the oral lesions has been variable and unpredictable. Topical and/or systemic steroids have been employed.

Pyostomatitis vegetans

Pyostomatitis vegetans is an unusual, but well-documented oral lesion that has been primarily associated with ulcerative colitis, but has been reported in a small number of cases of Crohn's disease.^8.9 It is considered a highly specific oral mucosal marker for inflammatory bowel disease.¹⁰ Generally a disease of adults, it may also occur in children.

Figure 10. Pyostomatitis vegetans — yellowish, slightly elevated, linear pustules on the gingiva that have the so-called "snail-track" appearance (courtesty of Dr. Mark Bernstein).

Pyostomatitis vegetans is characterized by the development of numerous 2-3 mm yellowish pustules as well as small vegetating or proliferating lesions on an erythematous mucosa that may undergo degeneration, ulceration, and suppuration (Figure 10). Necrotic lesions can be wiped off, leaving a hemorrhagic surface. The lesions often have a snail-track pattern.

Most areas of the mouth may be involved, including buccal mucosa, gingiva, hard and soft palate, and vestibule. The dorsal tongue, however, is rarely affected.¹⁰ Symptoms are not usually severe. In most cases, the bowel disease precedes the onset of oral lesions and the severity of the disease tends to parallel the activity of the bowel disease.¹¹ In some cases however, the gastrointestinal symptoms may be so mild as to remain undetected unless thorough inspection of the gastrointestinal tract is performed.^9,11

The histopathologic features of pyostomatitis vegetans are fairly consistent. The lesions show hyperkeratosis; acanthosis, which often results in a deep folding of the epithelium; and acantholysis. A dense cellular infiltrate of eosinophils and neutrophils is present throughout the epithelium and lamina propria. Small eosinophilic abscesses may be seen in the basilar portion of the epithelium and superficial lamina propria. A mixed infiltrate of polymorphonuclear neutrophil leukocytes, plasma cells, and lymphocytes is present in the connective tissue, often in a perivascular orientation. Direct and indirect immunofluorescence are usually negative.¹² Serum eosinophilia may also be present.

Recently, there have been reports of pyostomatitis vegetans presenting with primary sclerosing cholangitis and liver disease prior to any other manifestations of inflammatory bowel disease.^11,13 These cases may reflect a lack of long-term follow-up since the association of liver disease and inflammatory bowel disease is well-known, as is the association of pyostomatitis vegetans and inflammatory bowel disease. In either case, liver function monitoring should be pursued in every patient diagnosed with pyostomatitis vegetans.

Treatment of pyostomatitis vegetans has had variable success. Topical therapy has included the use of corticosteroid rinses, pastes, and ointments; tincture of iodine; and hydrogen peroxide. Systemic therapy has included corticosteroids, sulfasalazine, dapsone, and azathioprine. Interestingly, the oral lesions do not always regress when the colitis is controlled.¹²

Polyposis Syndromes

Gardner's Syndrome

Figure 11. Gardner's syndrome — osteoma of the maxilla (courtesy of Dr. Mark Bernstein). Figure 12. Gardner's syndrome — polyposis of the colon with multiple areas of adenocarcinoma (arrows).

Gardner's syndrome is inherited as an autosomal dominant trait. It is characterized by multiple adenomatous polyps of the colon and rectum, multiple osteomas, cutaneous epidermoid cysts, and fibromas. The osteomas most commonly occur within the jaws (Figure 11), particularly at the angle of the mandible, frontal bones, and within the frontal and ethmoid sinuses. They may cause facial deformities that necessitate removal. Supernumerary teeth, multiple odontomas, and impacted teeth have also been reported.

In most cases, the patient will have knowledge of the underlying condition; but, in some cases, the detection of the oral lesions initiates diagnosis. This is important because these patients have a high risk of colorectal carcinoma (Figure 12). Fifty percent of patients with Gardner's syndrome will develop colorectal carcinoma by age 30, and the risk approaches 100 percent in older patients.¹⁴

Diagnosis of an oral osteoma, particularly in the presence of a history of "skin tumors" or other oral findings, should elicit a suspicion of Gardner's syndrome and precipitate a thorough evaluation of the gastrointestinal tract for polyps. Genetic counseling would also be appropriate.

Peutz-Jeghers Syndrome

Figure 13. Peutz-Jeghers syndrome — cutaneous small, flat brown to gray pigmented lesions on the face with concentration in the perioral area.

This is an autosomal-dominant condition, although a number of cases will have no family history. It generally manifests in childhood and is characterized by benign polyps involving the entire intestinal tract in association with pigmented cutaneous and mucosal lesions. The pigmented lesions measure 1-5 mm and are often brown, although they may also be black or blue-gray. They are generally found in a perioral location (Figure 13) and on the dorsal surfaces of the fingers and toes. Intraorally, the lips, buccal mucosa, gingiva, and hard palate are most often involved. Skin lesions may fade with age but the oral lesions tend to become more prominent.¹

The prognosis for this condition is much better than for Gardner's syndrome in that the intestinal polyps are not premalignant. They may, however, lead to intussusception, which can result in infarction and peritonitis.

Author

Janice P. Handlers, DDS, is a professor of pathology at the University of Southern California School of Dentistry.

References

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11. Philpot HC, Elewski, et al, Pyostomatitis vegetans and primary sclerosing cholangitis: Markers for inflammatory bowel disease. Gastroenterology 103:668-74, 1992.

12. Chan SWY, Scully C, et al, Pyostomatitis vegetans: Oral manifestation of ulcerative colitis. Oral Surg Oral Med Oral Pathol 72:689-92, 1991.

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14. Neville BW, Damm DD, et al, Oral and Maxillofacial Pathology, 1st ed, WB Saunders Co, Philadelphia, 1995, p 473.

To request a printed copy of this article, please contact/Janice P. Handlers, DDS, Oral Pathology Associates, Inc., 11500 W. Olympic Blvd., Los Angeles, CA 90064.