Lecture 8 - Oral Medicine Aphthous Ulcers PDF

Aphthous Lesions Dr. Dilara Kazan Department of Oral&Maxillofacial Surgery Aphthous Ulcers/Stomatitis • The most common diseases of the oral mucosa. • The most probable mechanism is cellular-type immune response. • Ulcers usually present in the mobile, nonkeratinized part of the oral mucosa. • Aph...

Aphthous Lesions Dr. Dilara Kazan Department of Oral&Maxillofacial Surgery Aphthous Ulcers/Stomatitis • The most common diseases of the oral mucosa. • The most probable mechanism is cellular-type immune response. • Ulcers usually present in the mobile, nonkeratinized part of the oral mucosa. • Aphthous ulcers are classified into minor, major, and herpetiform types. • It may also represent a manifestation of systemic disease. • Aphthous ulcers or recurrent aphthous stomatitis (RAS) is one of the most common diseases of the oral mucosa, affecting 10 to 30% of the population. The exact etiology remains unknown. • Many predisposing factors have been implicated in the development of aphthous ulcers, including genetic predisposition, allergy, bacteria, viruses, iron deficiency, low levels of vitamin B12 and folic acid, hormonal disturbances, trauma, stress, etc. • According to clinical criteria, based on the size, number, depth of ulceration, duration, and scarring after resolution, aphthous ulcers are classified into minor, major, and herpetiform types. Aphthous Ulcers/Stomatitis • Minor • Most common clinical subtype representing approximately 80 to 85% of cases. • Clinical features • Clinically, recurrent painful ulcers 3 to 7 mm in diameter, with a yellowish bottom +pseudomembrane and red halo (narrow band of periulcer erythema) are observed . • Usual history is one or crops of several painful ulcers recurring at intervals of a few weeks. Aphthae typically affect only the non-keratinised mucosa, usually the labial and buccal mucosa, sulcuses, or lateral borders of the tongue. • Individual minor aphthae persist for 7–10 days, then heal without scarring. Often all ulcers in a crop develop and heal more or less synchronously. • Recurrences are common, with variable intervals of quiescence in between attacks. The diagnosis is based exclusively on clinical criteria. Aphthous Ulcers/Stomatitis • Major • Rare subtype of the disorder. It was previously known as recurrent periadenitis, or necrotizing disease of Sutton. • Clinical features • Clinically, it is characterized by large, circumscribed, and deep ulcers, 1 to 3 cm in diameter, with white-yellow surface and red inflammatory halo in the periphery, but size should not be an absolute criterion. • Sometimes subfebrile fever, LAP, induration • They are solitary or multiple (3–6), lasting 4 to 6 weeks. In cases where recurrent lesions develop often in the same site, after healing they may leave scarring and atrophy. This type may occasionally develop on keratinised mucosa. Ulcers can be designated as major form on the basis of either size or duration. • The pain of major aphthae can interfere with eating. • The lesions are found, most often, in the mucosa of the lip, buccal mucosa, tongue, and soft palate. Recurring time ranges from 1 to 3 months. The diagnosis is based on the clinical criteria. Herpetiform Ulcers • The vessels of the lamina propria are dilated and a mixed• A relatively rare clinical variety of aphthous ulcers. • The name derives from their clinical similarity with type inflammatory infiltrate consisting of lymphocytes, herpetic lesions in the mouth, although the two entities neutrophils, and histiocytes is present. have distinct histopathologic, microbiological, and immunologic differences. • Clinical features • Clinically, the lesions appear as tiny ulcerations, which progressively grow and swarm in groups, sometimes in the floor of mouth and ventral tongue • Ulcers are typically many (10–100); they have a diameter of 1 to 3 mm and are very painful. They are surrounded by erythematous halos and last for 1 to 2 weeks. The lesions recur frequently for period of 1 to 3 years. They may appear in any mobile area of the oral mucosa. The disease affects, most commonly, patients between ages 20 and 30. The diagnosis is based on the clinical characteristics. • Pathology • There are no diagnostic laboratory tests. Histologically, non- specific ulceration, covered by a fibrin membrane is observed. Aetiology • Immunological abnormalities • Possible aetiological factors for recurrent aphthae: • Genetic predisposition Aphthae lack virtually all features of typical autoimmune • There is good evidence for a genetic predisposition. The diseases. They also fail to respond reliably to family history is often positive, and the disease affects immunosuppressive drugs and become more severe in the identical more frequently than non-identical twins. No immune deficiency state induced by HIV infection. genetic marker has been found. In the possibly related Behçet’s disease, the evidence for a genetic predisposition • Gastrointestinal disorders is much stronger. Aphthae are only rarely associated with gastrointestinal disease such as coeliac disease, and then as a result of a • Exaggerated response to trauma deficiency secondary to malabsorption, particularly of There is some evidence that minor trauma is more likely to vitamin B12 or folate. develop into an ulcer in a susceptible individual, and most ulcers are on the less trauma-resistant lining mucosa. The • Haematological deficiencies Deficiencies of vitamin B12, folate or iron have been evidence for this is stronger in Behçet’s disease. reported in as many as 20% of patients with aphthae. • Infections In many such patients, the deficiency is latent, the There is no evidence that aphthae are directly due to any haemoglobin is within normal limits, and the main sign is microbes either causing infection or triggering immune micro- or macrocytosis of the red cells. In patients who thus reactions prove to be vitamin B12 or folate deficient, remedying the deficiency may bring rapid resolution of the ulcers. Aetiology • Hormonal disturbances • None completely explain the disease, but different In a few women, aphthae are associ- ated with the luteal factors may apply to different individuals or subgroups phase of the menstrual cycle, but there is no strong of patients. deficiencies of iron, folate or B are the 12 evidence. Pregnancy is often associated with remission. most significant predisposing factors because these may be secondary to another more significant condition and • Stress because addressing them may cure or ameliorate the Some patients relate exacerbations in times of stress, condition. and some studies have reported a correlation. • HIV infection Aphthous stomatitis is a recognised feature of HIV infection. Its frequency and severity are related to the degree of immune deficiency. • Non-smoking It has long been established that recurrent aphthae are a disease, almost exclusively, of non-smokers, and this is one of the few consistent findings. Recurrent aphthae may also start when smoking is abandoned. Diagnosis / Management • Diagnosis is almost exclusively by history, primarily •Management recurrences of self-healing intraoral ulcers at fairly regular •Apart from the minority with underlying systemic disease, intervals. Almost the only other condition with this history treatment is empirical and palliative only. is Behçet’s disease. Usually, increasing frequency of ulcers •No medication gives completely reliable relief. Lowbrings the patient to seek treatment. A detailed history of potency and topical agents should be tried first. Some the ulcer number, shape, size, site, duration, frequency of patients report that changing toothpastes is helpful. attacks is required. •Reassurance and education Patients need to understand that the ulcers may not be • Most patients appear well, but haematological curable but can be made bearable with symptomatic investigation is particularly important in older patients treatment. The condition usually wanes eventually of its and those with recent exacerbations in frequency of crops, own accord, although after many years. •Corticosteroids ulcer size or pain. • Routine blood indices are informative, and usually the Some patients get relief from hydrocortisone, 2.5 mg, most important finding is an abnormal mean corpuscular oromucosal tablets allowed to dissolve next to the ulcer volume (MCV). If macro- or microcytosis is present, further three times per day. These low-potency cortico- steroids investigation is necessary to find and remedy the cause. adhere to the mucosa to provide a high local concentration Treatment of vitamin B12 deficiency or folate defi- ciency of drug. They probably reduce the painful inflammation but is sometimes sufficient to control or abolish aphthae. do not speed healing much or reduce frequency of attacks. They are best applied in the very early, asymptomatic stages. Diagnosis / Management • Chlorhexidine • Treatment of major aphthae A 0.2% solution has also been used as a mouth rinse for Major aphthae, may sometimes be so painful, persistent aphthae. Used three times daily after meals and held in and resistant to conventional treatment as to be the mouth for at least 1 minute, it has been claimed to disabling. Reportedly effective treatments include reduce the duration and discomfort of aphthous azathioprine, cyclosporin, colchicine and dapsone, but stomatitis. thalidomide is probably most reliably effective. • Topical salicylate preparations However, such drugs can only be given under specialist Salicylates have an anti- inflammatory action and also supervision. have local effects. Preparations of choline salicylate in a gel can be applied to aphthae. These preparations, which are available over the counter, appear to help some patients. • Local analgesics These provide only symptomatic relief, but benzydamine mouthwash or spray helps some patients. Topical lidocaine or benzocaine sprays and gels are more effective but can only be used in limited doses and for a short time. BEHÇET’S DISEASE - Adamantiades • Behçet’s disease was originally defined as a triad of oral aphthous stomatitis, genital ulceration and uveitis.(+skinErythema nodosum) • However, it is a systemic vasculitis of small blood vessels and affects many more organ systems than suggested by this limited definition. • The importance of making the diagnosis is indicated by the life-threatening risk of thrombosis, of blindness or brain damage. • A chronic multisystemic and polysymptomatic disease with strong evidence supporting autoimmune pathogenesis. • Positive pathergy test occurs in 50 to 60% of patients. • Clinical • Behçet’s disease is particularly common in Turkey, central Asia, the Middle East and Japan but is less common in emigrants from these areas and is rare in those from Europe, the Americas and Africa. This matches the geographic incidence of the human leukocyte antigen (HLA) B51 allele. Aphthous ulcers may be present in all clinical subtypes. • Patients are usually young adult males between 20 and 40 years old. Patients suffer one of four patterns of disease: • Mucocutaneous Oral aphthae are the most consistent feature, are not distinguishable from common aphthous stomatitis and may be of any of the three types. There is often genital ulceration and a variety of rashes including erythema nodosum and vasculitis. Dermal lesions include papules, pustules, folliculitis, erythema nodosum, and more rarely necrotic lesions. BEHÇET’S DISEASE - Adamantiades • Arthritic Joint involvement with or without mucocutaneous involvement. The large weight-bearing joints are most affected. There is pain, but no destructive arthritis and only a few joints are involved. Asymmetric, poliarticular involvement. The pain may be relapsing or constant. • Neurological This type may occur with or without other features and is usually a late stage. Vasculitis within the brain causes a variety of neurological symptoms including sensory and motor disturbances, confusion. Thrombosis of vessels causes raised intracranial pressure, blurred vision and headache. • Ocular This type may also be solitary or accompany other types. There may be uveal inflammation or vasculitis and thrombosis of the retinal arteries, either of which can lead rapidly to blindness if not treated. Conjunctivitis, iridocyclitis with hypopyon, uveitis, and retinitis which can cause blindness. Aetiology / Diagnosis and management • The aetiology is unknown, but the disease has features including circulating immune complexes, high levels of cytokine secretion and activation of lymphocytes and macrophages in the circulation. These suggest an immune-mediated reaction, and it is presumed that this may be a response to an unknown infectious agent, possibly through immune cross reaction between pathogen and host heat shock proteins. • The racial distribution suggests a strong genetic component and HLA tissue types are linked, most strongly to HLA-B51. This is a common allele and so is not of use in diagnosis but can predict ocular lesions. • Diagnosis and management • There are no pathognomonic diagnostic tests. • Oral aphthae are frequently the first manifestation. Behçet’s disease should therefore be considered in the differential diagnosis of aphthous stomatitis, particularly in patients in a racial group at risk, and the medical history should be checked for the features. • As a result, there are no absolute criteria or reliable tests for the diagnosis, but in a dental setting, aphthous stomatitis in combination with any two of the other major features can be regarded as likely indicators meriting referral of the patient. Aetiology / Diagnosis and management • Tests are not helpful in diagnosis, apart from the the absence of these and other significant pathergy test. The skin-prick test is positive if there is complications, relapses become less frequent, and the an exaggerated response to a sterile needle puncture disease may eventually burn out. of the skin. However, the test must be interpreted by an experienced clinician and tends to be positive only in Mediterranean patients. Moreover, a positive pathergy test does not correlate with the presence of oral lesions or with the overall severity of the disease. It is also not entirely specific for Behçet’s disease. • Treatment is difficult and requires a multidisciplinary approach. Cyclosporin and tacrolimus are the main treatments, with steroids for acute exacerbations. Thalidomide or topical tacrolimus are most effective for oral ulcers. Anti- tumor necrosis factor (TNF)α drugs such as infliximab are a promising recent option, but a wide range of treatments are used for specific conditions. • Complications include blindness, rupture of largevessel aneurysms, thrombosis and embolism, but in