Earn 4 CE credits This course was written for dentists, dental hygienists, and assistants. Demystifying Recurrent Oral Ulcerations A Peer-Reviewed Publication Written by Michelle Hurlbutt, RDH, BS and Lane Thomsen, DDS, MS PennWell is an ADA CERP Recognized Provider Go Green, Go Online to take your course This course has been made possible through an unrestricted educational grant from Tom’s of Maine. The cost of this CE course is $59.00 for 4 CE credits. Cancellation/Refund Policy: Any participant who is not 100% satisfied with this course can request a full refund by contacting PennWell in writing. Educational Objectives include Behçet’s disease, inflammatory bowel disease, Sweet’s Upon completion of this course, the clinician will be able to syndrome, HIV infection, lupus, neutropenia, Mouth and do the following: Genital Ulcers with Inflamed Cartilage Syndrome (MAGIC) 1. Explain the etiology of oral ulcerations. syndrome, mucous membrane pemphigoid, pemphigus vul- 2. Describe the clinical features and symptoms of garis and erythema multiforme. It is essential that the clinician aphthous ulcers. understands the etiological factors and can perform a differen- 3. Conduct a differential diagnosis for recurrent tial diagnosis for RAU to treat the patient appropriately. oral ulcerations. 4. Outline the topical and systemic medications used in Signs and Symptoms of the treatment of recurrent aphthous ulcerations and Recurring Aphthous Ulcers other palliative care and recommendations for patients. Minor aphthous ulcers Abstract Minor aphthous ulcers are small and cause the least dis- Oral irritations and ulcerations occur frequently in the general comfort. They are most prevalent in people 10–40 years of population. Recurrent aphthous ulcers (RAU) are the most age. Usual locations include the floor of the mouth, buccal common. There are three types of RAU — minor, major and and labial mucosa, tip of the tongue, and ventral surface of herpetiform, the most common being minor aphthae. The the tongue. They are rare on the dorsum of the tongue and exact etiology of RAU is not known. Systemic and local fac- on keratinized mucosa. Patients may become aware of them tors, as well as infectious agents, have been proposed. Certain when a tingling or burning sensation occurs. Within two days, medications and foods are associated with oral ulcerations, a raised erythematous (red) papule or white spot appears. and chemicals such as sodium lauryl sulfate (SLS) contained This ulcerates, resulting in a pseudomembranous grayish or in dentifrices have also been implicated. RAU also occur in yellowish center within the lesion. Minor aphthae are round more serious systemic diseases and where appropriate patients or oval and measure up to 4 mm in diameter. They usually should be referred for screening and medical care. Treatment heal uneventfully seven to ten days after the first signs appear. of recurrent aphthous ulcers is palliative, based on the sever- Recurrence may take weeks or years.9,10 ity of the lesions. Both topical and systemic medications are Figure 1. Minor aphthous ulcer available. Nutritional and oral hygiene advice should also be given, and if patients are sensitive to SLS, a low-dose SLS or SLS-free dentifrice should be recommended. Introduction/Overview Oral irritations and ulcerations occur frequently in the gen- eral population and result in varying degrees of pain and debilitation for patients. Recurrent aphthous ulcers (RAU), also known as “canker sores,” are the most common.1 RAU occur in approximately 20% of the population, with greater prevalence in upper socioeconomic groups and nonsmokers.2 There are three types of RAU: minor, major and herpetiform. The most common are minor aphthae, accounting for at least 80% of all cases.3,4 Major aphthae account for approximately Major aphthous ulcers 10% of cases, and herpetiform less than 10%.5,6 Usually pa- Major aphthae (Sutton’s ulcers) are more severe than minor aph- tients only have one type.7 thae — larger, slower to heal and more painful — and can lead The second most common source of recurring oral ulcer- to adjacent and facial edema. They are found in all regions of ations is the herpes simplex virus (HSV-1). Oral ulcerations oral mucosa, including keratinized mucosa, and are often larger also result from infection by other viruses, including the HIV, than a centimeter in size. While they typically heal in ten to forty Coxsackie and ECHO viruses. Fungal and bacterial infec- days, in extreme cases healing can take months while new ulcers tions associated with oral ulcers are rarer and require extra are developing. Major RAU heal with scarring. If long-lasting consideration with respect to immunocompromised status.8 and frequently recurring, they can result in morbidity and poor Other ulcerative conditions include oral squamous cell carci- quality of life, with poor nutrition and stress.11,12 noma (SCC) and trauma-related lesions (thermal, chemical or physical). Prescribed medications are also associated with the Herpetiform aphthous ulcers development of oral ulcers. Extensive mucositis and stomati- Herpetiform ulcers occur as multiple lesions, up to 100 at a time, tis are seen in patients following head and neck radiation and and can range from <1 mm to 3 mm in diameter each. Herpe- chemotherapy. Systemic conditions involving oral ulcerations tiform RAU also coalesce into larger irregular lesions. Healing 2 www.ineedce.com Figure 2. Major aphthous ulcer drome often presents with classic RAU in addition to fever, erythematous skin lesions and neutrophil disorder.27 Gastrointestinal diseases associated with RAU include celiac disease and Crohn’s disease. Celiac disease (also known as celiac sprue or gluten-sensitive enteropathy) is character- ized by nutrient malabsorption and improves as gluten is withdrawn from the diet. The most common oral symptom is RAU. A recent study revealed that as many as 42% of celiac disease patients screened had oral soft tissue ulcerations, com- pared with 2% of the control group.28 With Crohn’s disease, Figure 3. Herpetiform aphthous ulcers RAU are the common oral manifestation; in a prospective study of 792 patients, RAU occurred in 10.6% of patients with the incidence slightly higher than with ulcerative colitis.29 Oral ulcers have been seen in 25%–45% of systemic lupus erythematosis (SLE) patients.30 SLE-related lesions are more apt to be on the hard palate and often improve with the treat- ment of other systemic and cutaneous SLE manifestations.31 Other conditions associated with oral ulcerations include (but are not limited to) mucous membrane pemphigoid, pem- phigus vulgaris, Reiter’s syndrome and erythema multiforme. Immunologic factors usually occurs in seven to ten days, without any scarring. Herpe- Some studies have suggested that RAU is a result of an abnor- tiform ulcers do not exhibit a vesicle stage and are not infectious. mal immune response. Increased concentrations of neutrophils in the ulcerative phase of the lesion suggest an active role in the Etiology of Oral Ulcerations pathogenesis or healing of RAU.32,33 Mast cells are able to release The exact etiology of RAU is not known. Systemic and local fac- a variety of mediators, including cytokines and proteinases, and tors, as well as infectious agents, have been proposed. Medica- have been shown to be 63% more numerous in RAU than in tions including nonsteroidal anti-inflammatory drugs (NSAIDs); healthy mucosa.34 A decreased ratio of CD4 to CD8 T-lympho- hypertensive medications such as ACE inhibitors, beta-blockers cytes has also been reported.35 Further research is needed to bet- with alpha-blocking activity and calcium channel blockers; and ter understand the relationship of RAU to immunoregulation. cyclosporine, interferons, penicillin, sulfonamides and nicorandil have all been implicated in oral ulcerations.13,14 ,15,16,17,18,19 Hematinic deficiencies The prevalence of iron, folic acid and B12 deficiencies and Systemic Factors and Conditions their role in RAU is not well understood. In recent studies, patients with RAU were found to have more hematinic defi- Genetic factors ciencies than did the control group, with low-serum vitamin More than 40% of patients with RAU may have a family his- B12 being the most common deficiency.36,37 tory of these ulcers.20 Patients with a positive family history tend to develop oral ulcers at an earlier age and have more Neutropenia symptoms than do other individuals.21,22 Genetically specific Neutropenia is characterized by an abnormally low count antigens, called human leukocyte antigen (HLA) subtypes, (<1,500 cells/mm³) of neutrophils in the peripheral blood. It is have been identified in patients with RAU; however, no de- often associated with clinical AIDS and lower CD4 cell counts, finitive association has been shown.23,24 and the risk for bacterial infection is a concern.38 Neutropenic ulcerations are often severe and can appear on the keratinized Syndromes and conditions and nonkeratinized tissue, and if the neutrophil count is not Systemic conditions associated with RAU include Behçet’s restored to normal, resolution is not as successful.39,40 disease, MAGIC disease, Sweet’s syndrome, inflamma- tory intestinal diseases and immunological factors. Behçet’s Hormonal disease is characterized by recurrent oral, ocular and genital The appearance of RAU may coincide with the menstrual ulcers and includes vascular, central nervous system and gas- cycle in a minority of women, but studies are contradic- trointestinal involvement. Of