Aphthous stomatitis: what is it, causes, symptoms, treatment

What is aphthous stomatitis?

Aphthous stomatitis - focal inflammation of the oral mucosa, in which round ulcers are formed (aphthae or erosion). Aphthae affect the inner surface of the cheeks, palate, tongue, become covered with a gray or yellowish coating, cause pain and discomfort. Usually the disease proceeds chronically, from time to time it aggravates, after 7-10 days it goes into remission.

Causes and risk factors

The cause of aphthous stomatitis is idiopathic and multifactorial, but is likely related to the activation of the cell-mediated immune system. Aphthous ulcers are not caused by acute infections and are therefore not contagious. Aphthous stomatitis can be caused by local trauma, emotional or physiological stress, allergies, or increased sensitivity (for example, to sodium lauryl sulfate, which is present in toothpaste and oral hygiene products, as well as such foods like cinnamon, cheese, citrus fruits, figs or pineapple), exposure to toxins (nitrates in drinking water), menstruation, or change the oral microbiome. The disorder may be present with 

intestinal malabsorption, enteropathy or celiac disease. Up to 20% of cases are associated with a deficiency of hematin (iron, folate, vitamins B6 and B12), although other deficiencies such as vitamin D, zinc or thiamine.

Epidemiology

Aphthous stomatitis affects approximately 20% of the general population. The disease is slightly more common in girls and women, and among wealthy socioeconomic classes and countries. Race is not a factor in disease. The age of debut may be in childhood, but more often in the second and third decades of life, becoming less common with age. Aphthous stomatitis can be a manifestation Behcet's syndrome, systemic lupus erythematosus, reactive arthritis or inflammatory bowel disease (especially Crohn's disease). These disorders can be ruled out based on systemic signs and symptoms.

Pathophysiology

Aphthous ulcers are initially and primarily the result of T cell mediated immune dysfunctions, but may also include neutrophil and mast cell mediated epithelial destruction mucous membrane. Lesions may have changes in several intercellular mediators, such as increased levels of interferon gamma, tumor necrosis factor alpha and interleukins (IL) -2, IL-4 and IL-5, as well as various adhesion molecules involved in cell communication and epithelial integrity. This inflammatory process leads to the formation of a pseudomembrane containing fibrinous exudate, bacteria, inflammatory cells and necrotic cells of the mucous membrane.

Aphthous ulcers occur on non-keratinized mucous membranes of the oral cavity, for example, along the lip or buccal surfaces, soft palate, floor of the mouth, ventral or the lateral surface of the tongue, the pharynx of the tonsils, free (marginal or loose) gums adjacent to the teeth, and the alveolar gums in the grooves of the upper and lower jaw. In contrast, herpes simplex virus (HSV) ulcers affect keratinized mucosal surfaces such as the adjacent gums and the dorsum of the tongue, lips, and hard palate.

Signs and symptoms

Patients may notice prodromal burning discomfort a day or two before the ulcers appear. Fever, rash, headache, or lymphadenopathy are usually absent and suggest another diagnosis such as herpangina or PFAPA syndrome (recurrent fevers with aphthous stomatitis, pharyngitis and lymphadenitis - from Periodic Fevers with Aphthous stomatitis, Pharyngitis and Adenitis). A history of previous ulcers is typical.

On physical examination, patients with aphthous stomatitis appear well and without fever. Clinical signs can be detected dehydrationespecially in infants and children. Eye damage (uveitis) or genitals suggests other diagnoses such as Behcet's syndrome or MAGIC syndrome (ulcers in mouth and genital with inflamed cartilage syndrome - from Mouth and genital ulcers with inflamed cartilage).

Ulcers of aphthous stomatitis are well-defined lesions with central necrotic an ulcer with a gray fibrinous exudate surrounded by an erythematous halo on a non-keratinized mucosa mouth. Typical sites include the mucous membranes of the cheeks and lips, the floor of the mouth, the ventral surface of the tongue, and the soft palate. Minor aphthous ulcers, the most common form of aphthous stomatitis, are less than 1 cm in diameter and are round or oval in shape, with a yellow or gray pseudomembrane surrounded by an inflammatory red halo, and usually heal within 7-14 days. Large aphthous ulcers are deeper, larger (often 2–3 cm in diameter), may have jagged raised edges, and may take many weeks or months to heal, sometimes scarring. Much less common are recurrent herpetiform aphthous lesions with a diameter of 1 to 2 mm in clusters of 10 to 100 in clusters or throughout the mouth, which usually heal within a few weeks.

Diagnostics

The diagnosis of aphthous stomatitis is clinical and laboratory testing is usually not required, although testing may be considered in persistent, severe, or recurrent cases.

Complete blood count showing anemia, may indicate a deficiency in hematin, such as iron, folate, or vitamin B12. Neutropenia may prompt cyclical neutropenia to be considered as the cause of ulcers.

Gluten-sensitive enteropathy (celiac disease) occurs in less than 5% of cases of recurrent aphthous stomatitis and can be identified by analysis of serum antibodies to endomysium and transglutaminase.

The possibility of testing for HIV in cases of complex or severe lesions, persistent herpetiformis or large aphthous stomatitis, as well as keratinization of the mucous membrane is being considered.

Treatment

The goals of treatment are to reduce pain (provide adequate hydration and nutrition), improve healing, and prevent relapses. Many treatment options are available for aphthous stomatitis, including local anesthetics (benzocaine), capping or occlusive agents (bismuth subsalicylate, sucralfate, octyl-2-cyanoacrylate and various bioadhesive emollient pastes), antiseptics (chlorhexidine and hydrogen peroxide), anti-inflammatory agents such as glucocorticosteroids (clobetasol, dexamethasone, fluocinonide and triamcinolone), amlexanox and metalloprotease inhibitors (antibacterial drugs of tetracycline series, doxycycline or minocycline), honey and immunomodulatory agents (amlexanox, colchicine, cyclosporine, cyclophosphamide, dapsone, methotrexate, montelukast, thalidomide or retinoids).

A phased approach to the management of aphthous stomatitis includes a primary local anesthetic and occlusive or antiseptic agents to relieve symptoms in minor cases. First-line treatment of major or minor aphthous stomatitis with significant symptoms typical for topical application of steroids in a gel or emollient paste for contraction duration. Another option is a one-time local injection of a steroid such as triamcinolone. Severe refractory or persistent cases can be additionally treated with systemic steroids (dexamethasone or prednisone), immunomodulatory agents (listed above), pentoxifylline or quercetin.

Experimental treatments may include various herbal products or topical drying (for example, tincture of benzoin), moxibustion (for example, applying silver nitrate) or even a biopsy - and all this after local anesthesia. Laser therapy can be effective in severe or recurring cases. Good oral hygiene can prevent relapses. Supplementation with iron, zinc, or vitamins B1, B2, B6, B12, or C may be beneficial for patients with deficiencies. A gluten-free diet is only important for people diagnosed with celiac disease.

Forecast

By definition, there is no major underlying medical condition and, most importantly, ulcers do not represent oral cancer and are not infectious. However, aphthae can cause significant discomfort. There is a spectrum of severity, with symptoms ranging from minor discomfort to disability. In severe cases of aphthous stomatitis due to pain while eating, weight loss may result from not eating. The illness usually lasts for several years before disappearing spontaneously at a later age.