DIFFERENTIAL DIAGNOSIS OF ACUTE AND CHRONIC SYMPTOMATIC ORAL ULCERATIONS Acute and chronic ulcerations represent the most common symptomatic mucosal pathoses encountered by oral health care practitioners. Every clinician should have an organized approach to these problems which will be encountered frequently. The first step in all cases should be to divide and conquer. The ulcerations can be classified as acute or chronic, and this will cut in half the number of diseases in the differential diagnosis. Acute lesions arise rapidly (1 or 2 days), normally heal in 10-14 days and may recur at varying intervals. In some cases, the lesions may take longer than a month to heal, but this is not typical. Recurrences are highly variable. Some may never recur, while others may recur before the first crop has healed. On the other hand, chronic erosions tend to slowly evolve and become more problematic over an extended period of time. Instead of crops of lesions interspersed with periods of remission, the chronic erosions tend to persist with variable levels of intensity. Patients rarely present to their health care professional when these lesions first arise; the vast majority of chronic ulcerations have been present for months when the patients present for diagnosis and treatment. Normally, the distinction between acute and chronic ulcerations is made easily; but like everything else, there are gray areas. Prior to the development of a differential diagnosis, the patient’s medical history should be evaluated thoroughly. The presence of any extraoral lesions must be documented. A listing of all utilized prescription and “over-the-counter” medications is mandatory. The following is a list of common symptomatic oral ulcerations: ACUTE CHRONIC Recurrent aphthous stomatitis Erosive lichen planus Herpangina Mucous membrane pemphigoid Hand, foot & mouth disease Pemphigus vulgaris Behçet's syndrome Lupus erythematosus Herpes simplex Drug reaction Herpes zoster Contact reaction Erythema multiforme Graft-versus-host disease Necrotizing sialometaplasia Cinnamon reaction Damm Sore Mouth 2 ACUTE ORAL ULCERATIONS 1. Recurrent Aphthous Stomatitis Recurrent aphthous stomatitis (RAS) is the most common pattern of oral ulcerations encountered by the health professional. Approximately 20 percent of the general population has a positive history for these ulcerations. Prevalence as high as 55% has been reported in populations under stress (professional school students). Numerous studies have indicated an immunologic cause. Although the humoral system is involved, the cell mediated immune response has received the most attention and is thought to be responsible for the initiation of the ulceration. Early lesions do show similarity to a delayed hypersensitivity reaction. Investigators theorize RAS is the result of bacterial toxins, foods, and other substances acting as allergens or haptens which initiate an immune response. A variety of allergens most likely is responsible. In addition, mucosal thickness and immunodysregulation appears involved in many patients. Elimination of one allergenic source often resolves RAS in some patients but not in others. Since discovery of the causative agent is most difficult, therapy has been directed toward decreasing the immune reaction. The prototypical and most common form is the minor aphthous stomatitis (MiRAS). These arise almost exclusively on nonkeratinized movable mucosa and exhibit yellow fibrinopurulent membranes surrounded by erythematous halos. The ulcerations vary from 2-10 mm (majority approximately 5 mm) and usually heal without scarring within 10-14 days. The recurrence rate is highly variable. The lesions may number from one to a hundred at a time. Several systemic medical problems can result in lesions clinically identical to RAS and must be ruled out in all cases which are severe or nonresponsive to therapy. A number of systemic disorders such as blood dyscrasia (esp. leukopenia), nutritional deficiencies (low zinc, iron, B12 or folate), Behçet's syndrome, Crohn's disease, celiac sprue and AIDS are associated with an increased prevalence of aphthous-like ulcerations. In addition, every one of the other acute ulcerative conditions may resemble RAS and must be ruled out prior to therapy. Topical steroids appear to be the most consistently efficacious; chemical cautery is contraindicated. Most over- the-counter medications produce more problems than they solve. If clinical contraindications to steroids exist (children, pregnancy, nursing, hypertension, diabetes, granulomatous infectious disease, G.I. ulcerations, blood dyscrasia, previous malignancy, etc.), permission for corticosteroid utilization must be obtained from the attending physician or utilize antimicrobials such as tetracycline or chlorhexidine. In all severe cases and those resistant to normal therapy, a systematic evaluation for the underlying trigger or any related systemic disorders should be performed. THERAPY Localized -Lidex gel (Sore Mouth Solutions [SMS] 1-1). Easy to apply but slightly bitter -Diprolene ointment (SMS 1-2). Thicker than gel but tasteless. Also available as gel but slightly bitter. Often prescribed generically due to difficulty to obtain 15gram tube. Diffuse -Dexamethasone solution (SMS 1-6) Damm Sore Mouth 3 Another type which exhibits significantly more morbidity is the major aphthous stomatitis (MaRAS). This variant also has been called periadenitis mucosa necrotica recurrens or Sutton’s Disease. These ulcerations are similar to MiRAS but are significantly larger, deeper, take longer to heal and result in scarring. The lesions are seen predominantly on movable mucosa, vary in size from one to several centimeters and often take up to six weeks to heal. It is not uncommon for a new lesion to arise before the current ulcer has healed. Long periods of remission are difficult to obtain. The usual topical steroids normally are ineffective. More potent local steroids (Kenacort® tablets, Kenalog 40® Injection, dexamethasone solution) or systemic prednisone often are required for temporary control. All MaRAS patients should be thoroughly evaluated to rule out a systemic basis for their ulcerations. THERAPY Accessible (vestibule, buccal mucosa, etc.): Kenacort tablets (SMS 1-9) Inaccessible (soft palate, tongue, etc.): Compounded dexamethasone solution (SMS 1-7) Extension past wet line: Kenalog 40 injection (SMS 1-10) A relatively rare variant is the herpetiform aphthous stomatitis (HeRAS). These ulcerations appear similar to MiRAS but generally are smaller in size, more numerous and can be found on movable or bound mucosa. The typical size is 2 mm or less, and it is not uncommon for patients to exhibit more than 100 lesions at one time. The recurrences are spaced so closely that the patients are seldom free of these very painful lesions and often have the ulcerations continuously for several years. The lesions frequently cluster and superficially may resemble a primary herpetic infection; the lack of a painful and intensely erythematous gingiva combined with the recurrence history allows separation. Therapy with 2% tetracycline rinse has proved efficacious but, on occasion, is not effective or becomes ineffective with time. A topical corticosteroid is the treatment of choice. 2. Herpangina This is a specific viral infection which can be caused by any one of a number of strains of enterovirus. It normally is seen in young children but may occur in older patients. Once infected, permanent immunity to the infecting strain develops, but an individual can have the disease several times from different strains. By adulthood, most individuals exhibit immunity to several strains. Affected patients present with sore throat, low-grade fever, headache, sometimes vomiting and abdominal pain. The lesions closely resemble RAS and most commonly occur on the soft palate, pharyngeal wall and tonsillar pillars. They normally heal within a week. THERAPY OTC ibuprofen and Sucrets® with dyclonine 3. Hand, Foot & Mouth Disease This is another clinical presentation of enterovirus infection which can be caused by one of several strains. The majority of the cases arise in young children but can present in adulthood. Damm Sore Mouth 4 It is characterized by an erythematous maculopapular rash of the skin which most frequently involves the hands, feet, legs, arms and buttocks. Anorexia, low-grade fever, coryza, sometimes lymphadenopathy, diarrhea, nausea and vomiting can occur. Oral lesions are invariably present and are the principal symptoms in over 90% of the patients. The lesions resemble RAS and occur primarily on the palate, tongue and buccal mucosa. The infection resolves within 10-14 days. Treat like herpangina. 4. Behçet's Syndrome This is a systemic abnormality which most likely is autoimmune and usually arises be- tween the ages of 10 and 45. It is 5-10 times more common in males. Oral, genital, skin and ocular lesions are seen. The oral lesions present as RAS, and the genital ulcers often are small and occur on the scrotum, root of penis, labia majora or perianally. Ocular lesions range from conjunctivitis to uveitis to hypopyon. The skin lesions usually present as pustules on the trunk, limbs or genitalia. A number of other systemic complications may occur also. Classic triad: oral ulcers, genital ulcers and ocular inflammation. If discovered, refer to an experienced dermatologist. 5. Herpes Simplex Infections Classically, herpes simplex is divided into type I in which the infections arise above the waist and type II which is seen below