Aphthous ulcers

Pharmacologic agents are among the most common causes of recurrent aphthous ulcers.

Can be cured with home remedies, and prescription and OTC topical and oral medication.

Apremilast may be effective for recurrent aphthous stomatitis.

No gender predilection.

Peak age of onset between ten and nineteen years.

Most commonly affects young adults, with the prevalence as high is 60% in students, decreasing in frequency and severity after age 50.

About 80% develop the condition before the age of 30.

More common among Caucasians than blacks

Characterized by the repeated formation of ulcers in the mouth, in otherwise healthy individuals.

Ulcers occur periodically and heal completely between attacks.

Symptoms range from a minor interference with eating and drinking to severe debilitating forms.

The cause is not completely understood.

Sometimes it manifests secondary to underlying infections, inflammatory, immunologic, or nutritional disorders.

Related to a T cell-mediated immune response, triggered by a variety of factors.

Precipitating factors include nutritional deficiencies, local trauma, stress, hormonal influences, allergies, and a genetic predisposition among other factors.

Affects about 20% of the general population to some degree.

More common in developed countries.

Most aphthae appear on the non-keratinizing epithelial surfaces in the mouth.

Classified as a type of non-infectious stomatitis.

Classified based on the size and evolution of the lesions into three forms: mine aphthae, major apthae and herpetiform ulcerations.

Complex apthosis refers to persistent presence of three or more ulcers, associated genital lesions, and result in serious disability, in the absence of Behcet disease.

Common simple aphthae accounts for 95% of cases, with 3–6 attacks per year, rapid healing, minimal pain and restriction of ulceration to the mouth.

Complex aphthae accounts for 5% of cases, where ulcers may be present on the genital mucosa in addition to mouth, healing is slower and pain is more severe.

The more severe forms may also involve keratinizing epithelial surfaces.

These ulcerations are round, crateriform, white-yellow depressions surrounded by a rim of erythema.

The  size of an aphthous ulcer may vary from 1-3 mm (aphthous minor, approximately 80% of cases) to larger than 1 cm (aphthous major, approximately 15% of cases).

 

Patients may have outbreaks of multiple ulcerations at one time. 

 

 These are usually quite painful but typically are self-limiting and resolve in 7-10 days for aphthous minor and 14-21 days for aphthous major lesions. [

Aphthous ulcers generally last about 7–10 days,.

Ulceration episodes occur about 3–6 times per year.

Aphthous stomatitis process usually starts during childhood or adolescence.

The condition usually lasts for several years before gradually disappearing.

Not associated with systemic signs or symptoms.

Local symptoms may include sensations such as burning, itching, or stinging that may precede the appearance of any lesions.

Pain may be out proportion to the extent of the degree of ulceration and is worsened by physical contact, especially with acidic food and drink.

No cure exists.

Treatments aim to manage pain, and promote healing.

Pain is worst during the initial formation of the ulcer, and then recedes as healing progresses.

Depending on the site of involvement speaking and chewing can be uncomfortable, and odynophagia or painful swallowing can occur.

In patients with severe disease, characterized by new lesions developing before old ones have healed may cause debilitating chronic pain that prevents adequate nutrient intake, leading to malnutrition and weight loss.

Lesions typically begin as erythematous macules which develop into ulcers that are covered with a yellow-grey fibrinous membrane that can be scraped away, and are surrounded by an erythematous halo.

Lesions appear to be non-contagious, non-infectious and not sexually transmissible.

The mucosal tissue destruction is thought to be the result of a T cell mediated immune response involving the generation of interleukins and tumor necrosis factor alpha.

Mast cells and macrophages are also involved, and also secreting TNF-alpha.

Aphthous ulcer histologic appearance shows an inflammatory infiltrate, 80% of which is made up of T cells.

The ratio of CD4+ T cells to CD8+ T cells in the peripheral blood of individuals with aphthous stomatitis is decreased.

No association between aphthous stomatitis and autoimmune diseases.

T cell-mediated mechanism of mucosal destruction is suggested.

Possible triggers include primary immuno-dysregulation, decrease of the mucosal barrier and states of heightened antigenic sensitivity.

At least 40% of people with aphthous stomatitis have a positive family history.

People genetically predisposed to aphthous stomatitis include those with HLA-B12, HLA-B51, HLA-Cw7, HLA-A2, HLA-A11, and HLA-DR2 human leukocyte antigen types.

However, these HLA types are inconsistently associated with this process and vary according to ethnicity.

Patients with a positive family history have a tendency to have a more severe form of the disease and have an early age of onset then is usual.

Stress has effects on the immune system and correlates with ulceration.

Aphthous-like ulceration also occurs in systemic immuno-dysregulation, as seen cyclic neutropenia and human immunodeficiency virus infection.

The thickness of the mucosa is an important factor in aphthous stomatitis as ulcers form on non keratinizing mucosal surfaces in the mouth, and decreases in the thickness of mucosa increase the frequency of occurrence, and factors which increase its thickness correlate with decreased ulceration.

Categorized into three distinct forms, based in size and number of ulcers:  minor, major, and herpetiform aphthous stomatitis.

Minor abscess stomatitis makes up approximately 80% of all recurrent aphthous stomatitis ulcers, and is typically found in nonkeratinized oral mucosa:labial mucosa, buccal mucosa, ventral surface of the tongue, and floor of the mouth.

Associated nutritional deficiencies associated with aphthous stomatitis include B12, folate, and iron, as all can cause oral mucosa atrophy.

Minor aphthous ulcers are painful, round or oval areas of ulceration, less than 1 cm in diameter, and covered with a gray white fibin layer, encircled by an erythematous ring.

Minor recurrent aphthous stomatitis usually heals without scarring within 7 to 10 days.

Major aphthous stomatitis is the most severe variant, accounting for 10 to 15% of recurrent aphthous stomatitis lesions.

Major aphthous,stomatitis lesions are greater than 1 cm and may persist for longer than four weeks and frequently result in scarring.

Major aphthous stomatitis lesions typically emerge in clusters of 1 to 3 on the lips, oropharynx and soft palate.

Herpetiform aphthous stomatitis is the least common form and characterized by small ulcerations that oftenmerge to create a larger, irregularly shaped ulceration.

These lesions typically resolved within 7 to 14 days and do not cause scars.

Local trauma is also associated with aphthous stomatitis as it decreases the mucosal barrier.

Dental manipulations, injections of local anesthetic in the mouth, frictional trauma from a sharp surface in the mouth such as broken tooth, or tooth brushing can decrease the mucosal barrier and increase risk of aphthous ulcers.

It is controversial whether hormonal factors are capable of altering the mucosal barrier and the likelihood of aphthous ulcerations.

Aphthous stomatitis is uncommon in smokers as tobacco use is associated with an increase in keratinization of the oral mucosa.

Theorized the process represents heightened sensitivity to antigenic stimuli, with cross-reactivity of the resulting cell-mediated immune response with cells of the epithelium, or caused by expression of HLA class II antigens which results in them being recognized by the immune system as foreign cells rather than self.

Other antigenic triggers may include streptococci, herpes simplex virus, varicella-zoster virus, adenovirus, and cytomegalovirus, although no evidence exists to confirm this.

Food allergy may precipitate aphthous ulcers in some cases.

Sodium lauryl sulphate is a detergent present in some brands of toothpaste and oral healthcare products, and may be associated with produce oral ulcers.

Aphthous ulcers are more common in people using toothpastes containing sodium lauryl sulphate.

Systemic disorders associated with aphthous-like ulceration include: Behçet’s disease, celiac disease, cyclic neutropenia, IgA deficiency, HIV, Inflammatory bowel disease, Sweet’s syndrome, Reiter’s syndrome, erythema multiforme, and other Immunocompromised states.

Aphthous-like ulcerations are clinically and histopathologically identical to the lesions of aphthous stomatitis.

Systemic illnesses with aphthous-like ulcers may also have ulcerations on other mucosal surfaces such as the conjunctiva or the genital mucous membranes.

MAGIC syndrome, mouth and genital ulcers with inflamed cartilage refers to relapsing polychondritis and is a possible variant of Behçet disease, and is associated with aphthous-like ulceration.

PFAPA syndrome tends to occur in children (Periodic Fever, Aphthous ulcers, Pharyngitis and cervical Adenitis).

Cyclic neutropenia may be associated with aphthous-like ulceration.

Gastrointestinal disorders are sometimes associated with aphthous-like stomatitis include: Celiac disease, and inflammatory bowel disease such as Crohn’s disease or ulcerative colitis related to nutritional deficiencies caused by malabsorption

Diagnosis is based on the clinical appearance and the medical history

of recurrent, self healing ulcers at fairly regular intervals.

Recurrent oral ulceration has few causes: aphthous stomatitis, Behçet’s disease, erythema multiforme, ulcerations associated with gastrointestinal disease, and recurrent intra-oral herpes simplex infection.

Tissue biopsy is not usually required as the histopathologic appearance is not pathognomonic, but shows a central zone of ulceration covered by a fibrinous membrane.

Tissues deep to the ulcer have increased vascularity and an inflammatory infiltrate composed of lymphocytes, histiocytes and neutrophils

Minor aphthous ulcerations are the most common type of aphthous stomatitis, accounting for about 80% of all cases.

Minor aphthous ulceration lesions are generally less than 10 mm in diameter.

Minor aphthous ulceration lesions affect non-keratinized mucosal surfaces such as labial and buccal mucosa, lateral borders of the tongue and the floor of the mouth.

Minor aphthous ulceration lesions usually are multiple, but single ulcers may occur.

Healing of minor aphthous ulceration lesions usually takes seven to ten days.

Healing of such lesions leaves no scar.

Usually between episodes of ulceration, an ulcer-free period of variable length is described.

Major aphthous ulceration subtype makes up about 10% of all cases of aphthous stomatitis, and the lesions are similar to minor aphthous ulcers, but are more than 10 mm in diameter and the ulceration is deeper.

Major aphthous ulcerations being larger, healing takes longer,about twenty to thirty days.

Major aphthous ulcerations may leave scars.

Subsequent episodes of ulceration usually is associated with a greater number of ulcers.

Major aphthous ulceration episodes occur more frequently than seen in minor aphthous stomatitis.

Major aphthous ulceration usually affects non keratinized mucosal surfaces.

Major aphthous ulceration can less commonly involve keratinized mucosa such as top surface of the tongue, gingiva or the soft palate or the back of the throat.

Herpetiform ulcers is a subtype of aphthous stomatitis with lesions resembling a primary infection with herpes simplex virus, but is not caused by herpes viruses.

Unlike true herpetic ulcers they are not preceded by vesicles.

Herpetiform ulcers are less than 1 mm in diameter and occur in crops from up to one hundred at a time.

Herpetiform ulcers may merge to form larger areas of ulceration.

Herpetiform ulcers heal within fifteen days.

Herpetiform ulcers may affect keratinized mucosal surfaces in addition to non keratinized ones.

Herpetiform ulcers are often very painful.

Herpetiform ulcers tend to recur more frequently than minor or major aphthous ulcers, and may be so frequent that ulceration seems continuous.

Herpetiform ulcers generally occurs in a slightly older age group than the other subtypes, and females are affected slightly more frequently than males.

Most patients with aphthous stomatitis have minor symptoms and require no specific therapy as the pain is tolerable with simple dietary modification of avoiding spicy or acidic foods and beverages.

No therapy is curative and topical and systemic medications have little or no efficacy.

Topical covering agents / barriers may reduce pain, and topical antiseptics may speed healing and prevent secondary infection.

Topical corticosteroids may reduce inflammation and are the mainstay management.

Systemic treatment is usually reserved for severe disease, but no single systemic intervention is effective.

Provision of good oral hygiene is important to prevent secondary infection.

Apremilast may be efficacious in management.

Amlexanox applied topically is effective in promoting healing.

Vitamin B12 supplementation and the avoidance of sodium lauryl sulfate in toothpaste may prevent recurrences, but data is not conclusive.

When ulceration associated with the menstrual cycle use of an oral contraceptive, or a progestogen may be beneficial.

Reducing mucosal trauma by avoiding rough foodstuffs and by brushing teeth with care.

Surgical excision of aphthous ulcers is ineffective.

Many treatments of unproven effectiveness exist: herbal remedies, and alternative treatments.

Topical triamcinolone reduces recurrent ulcers by 28%.

Laser therapy can alleviate symptoms and promote also healing.

Patients with severe aphthous stomatitis may benefit from systemic corticosteroids, Colchicine, azothioprine, dapsone, thalidomide, and pentoxifylline that may reduce symptoms, improve healing, or decrease recurrence rate.

Natural extracts such as curcumin, and honey may reduce size of oral lesions.

Probiotics are reported to reduce oral pain.