Aphthous ulcer and aphthosis 

I-Introduction

Canker sores, described by Hippocrates in 400 BC, are usually located on the oral and pharyngeal mucosa, and can also be observed in the genital region.

 The primary lesion is an ulceration from the outset, due to tissue necrosis. 

It can leave a scar after healing. Canker sores are located on non-keratinized epithelia;

The recurrent nature of several canker sores (several outbreaks per year) defines an aphthosis. These canker sores can be isolated or part of certain systemic diseases that can affect different parts of the body.

II – Definition

Aphtha is a superficial round or oval ulcer with a fibrinous base of “fresh butter” color surrounded by a carmine red halo, the edges are edematous, without induration at the base.

Oral aphthosis is a classically recurring condition of the oral mucosa that develops in flare-ups. It generally leaves no after-effects.

Remember that a canker sore is a symptom and aphthosis is a disease.

III- Epidemiology

• Prevalence: 10 to 65%
• Aphthosis begins in individuals aged 10 to 20 years.
• Family History ++
• Frequency and severity of recurrences with age
• Incidence in women and socioeconomically advantaged classes 
• In children: Oral lesions are the most common.
• Girls ++

VI- etiologies

Several factors appear to be involved:

1. Physiological factors 

A. Genetic factors:

• Several variants of DNA polymorphisms have been implicated in the occurrence of aphthous lesions. Especially those of the genomes coding cytokines (IL-2, IL-6, IL-10, TNFα).

B. Hormonal factors

• Cyclic episodes of oral aphthosis have been observed in women during premenstrual hormonal changes; these outbreaks of aphthous ulcers disappear during pregnancy and reappear after childbirth.

C-Psychological factors.

• A correlation has been shown between stress and the appearance of aphthous lesions. 
• Students during exam periods would actually present a higher percentage of injuries than that observed during vacation periods. 

2. Environmental factors

A. Power supply

Some foods can cause the appearance of aphthous lesions and thus increase the frequency of aphthosis; among these foods are: cow’s milk, cheese, chocolate, nuts and dried fruits and acidic fruits, mustard, spices, cabbage, honey, coffee…

B. Medications

Drugs may cause aphthoid lesions; the most commonly reported in the literature are:

• Anti-inflammatories,
• Gold salts: indicated for patients suffering from rheumatism,
•  Nicorandil: vasodilator used for cardiac pathologies 
• Captopril, used for the treatment of high blood pressure.
• Some antiepileptics: Carbamazepine, Hydantoin and barbiturates,
• Methotrexate, folic acid antagonist (vit B9), used for certain types of cancers, RA 

• Alendronate: treatment of postmenopausal osteoporosis,
• Sodium hypochlorite: antiseptic,
• Sodium lauryl sulfate: found in some toothpastes.

 C. Poor oral hygiene:

A significant correlation exists between the severity of canker sores, their number, their recurrences and poor oral hygiene.

D. Nutritional deficiencies: 

A deficiency in iron, folic acid and vitamin B12 can promote the appearance of aphthous lesions.

3. Immuno-allergic factors: 

• Some patients develop hypersensitivities to certain foods. Indeed, Besu et al . reported the presence of a strong association between high levels of anti-cow’s milk immunoglobulins A, E and G and aphthous manifestations. Patients may then present other manifestations affecting the digestive tract.

4-Associated systemic factors: 

• Hemopathies
• Behcet’s disease
• Chronic inflammatory bowel diseases
• Celiac disease
• Human immunodeficiency virus infection
• Sutton’s periadenitis
• MAGIC syndrome
• PFAPA syndrome
• Sweet’s syndrome
• Systemic lupus erythematosus
• Reiter’s syndrome

V-Pathogenesis 

The pathophysiology of aphthous lesions is not completely elucidated, hence their qualification as idiopathic in most cases. Several hypotheses have been put forward to try to explain the occurrence of aphthous lesions. They are mainly based on non-specific observations.  

1-inflammatory abnormalities:

 Aphthous ulceration appears to be due to a cytotoxic action of CD4+ and CD8+ T lymphocytes and monocyte-macrophages.

2-microbial theory:

Aphthous ulcer is not an acute infectious disease.

The presence of certain infectious agents was nevertheless noted. 

• Streptococci and their toxins
• Helicobacter pylori
•  some viruses such as HSV, CMV, HIV

VI- clinical study

Aphtha is the common symptom of several clinical forms that can be classified into:

• The common “vulgar” mouth ulcer.
• Recurrent oral aphthosis.
• Aphthous diseases or oral aphthosis associated with other general locations (e.g. genital aphthosis).

1. The common “vulgar” mouth ulcer

1.1. Location:

• Canker sores occur in areas of the mouth where the mucosa is not keratinized and not adherent to the underlying layers.
• The masticatory mucosa of the hard palate and the maxillary and mandibular alveolar rims are most often spared.

1.2. Training:

The course of a mouth ulcer can be schematically divided into four phases according to Stanley:

• The prodromal phase.
• The pre-ulcerative phase.
• The ulcerative phase.
• The re-epithelialization phase.
• The prodromal phase: less than 24 hours

It is painful with tingling or burning sensations, no apparent clinical lesion.

• The pre-ulcerative phase: from 18h to 72h 

During which one or more erythematous, macular or papular lesions develop, or perhaps even vesicular (ephemeral vesicles that are most often unnoticed), with increasing pain.

• The ulcerative phase : from 72 hours to 16 days

The canker sore ulcerates, in a punctiform or lenticular manner, but never bleeds.

• The re-epithelialization phase : from 4 days to 35 days

Painless, canker sores usually heal without scarring.

1.3 Description :

• Inflammatory ulceration of varying diameter from 2 to 10 mm.
• Their edge is clear, with a bright red inflammatory peripheral border. 
• A yellowish necrotic background, “fresh butter”, then grayish. 
• The base, very slightly edematous, remains flexible and not hardened.

• They are locally painful, uncomfortable, and interfere with speech and eating.
• Persist for 1 to 2 weeks, typically without satellite adenopathy, and gradually disappear without leaving a scar.

2. Recurrent oral aphthosis:

There are two different classifications for aphthous ulcers:

• According to morphology: 

• Minor aphthosis
• Miliary aphthosis 
• Major aphthosis 
• According to severity:

• Simple aphthosis 
• Complex aphthosis. 

2.1 Minor form of recurrent oral aphthosis (RAA)

• The minor form of ABR is the most common variety, especially in children.
• It mainly affects people between the ages of 10 and 40. 
• It is characterized by the presence of mouth ulcers less than 1 cm in diameter, isolated (common mouth ulcer) or multiple (2 to 5). 
• They heal in 7 to 15 days without scarring. 
• They recur after an interval of 1 to 4 months. Canker sores can also appear continuously without a free interval between them.

2.2 Major form of recurrent oral aphthosis

• It is more severe but rarer.
• Aphthous ulcers are also described as “necrotizing aphthous ulcers.”
•  It is composed of single or multiple (2 to 6) canker sores, 1 to 3 cm in diameter, surrounded by edema.
• Localized over the entire surface of the oral cavity and may extend to the oropharynx with a predilection for the soft palate.
• It lasts up to 6 weeks, and often leaves a scar.
• Its periodicity is random: long periods of remission and intense activity can alternate at an unpredictable rate.

2.3 Herpetiform form of recurrent oral aphthosis

• Also described by the terms miliary aphthae or Cooke’s herpetiform ulcers.
• These lesions are small (1 to 2 mm), their number in each outbreak varies: from five to 20 elements, and can reach up to 100 elements.
• These ulcers do not have an erythematous border and can be confused with a primary herpes infection.
• These ulcers are grouped together and tend to merge due to their size; they heal in 7 to 30 days.
• They may recur so frequently that ulcerations may be virtually continuous.

2.4 Simple form of recurrent oral aphthosis

• It is marked by the very rare development (less than 7 outbreaks per year) of episodes of well-defined moderate ulcerations limited to the oral cavity which tend to heal in one to two weeks at most.

2.5 Complex form of recurrent oral aphthosis:

• It is characterized by more frequent episodes of continuous and persistent ulcerations that heal very late and have pronounced symptoms.
• It is found in association with a systemic condition (eg: Behçet’s disease, HIV, etc.).

3. Aphthosis in the context of general diseases:

Behçet’s disease (BD):

• It is a recurrent inflammatory multisystem disease represented by chronic systemic vasculitis.
• There are no additional biological criteria.
• There is no pathognomonic examination for MB and the diagnosis is based on clinical criteria: cutaneous-mucosal, ocular, articular, others.

Diagnostic criteria of the International Criteria for Behçet’s disease

The diagnosis is made when the patient has a score greater than or equal to 4 points after excluding other pathologies.

a-Cutaneo-mucosal manifestation

1. Oral aphthosis

– Present in 98% of cases.

– Constitutes a major criterion for the diagnosis of the disease.

– It is observed in 3 forms, their number is from 1 to 100, and their location is variable, round in shape, with a clear and erythematous outline, covered with a grayish-white fibrinous coating.

– Characterized by the absence of the prodromal phase

2- Genital aphthosis 

– Present in 60 to 65% of cases. 

– Its appearance is generally identical to that of oral aphthosis, but with irregular contours and slow healing.

– His relapses are less frequent. 

– Leaving an indelible scar allowing a retrospective diagnosis to be made.

       3-Skin ulcers

– It is rare 3% 

– Is seen especially in the fold areas.

– Observed especially in children.

– Leaving a scar.

4- Pseudofolliculitis:

– Frequent (60% of cases).

– Located on the back, face, lower limbs and buttocks.

– These are papules that become pustules in 2 to 3 days, which become covered with a crust that comes off without leaving a trace.

They are not centered by a hair.

b- Ocular manifestations

Ocular involvement is one of the major criteria for Behçet’s disease. It presents as a recurrent, hyperacute inflammation of the eye, described as uveitis. It progresses in flare-ups with bilateral lesions.

 Uveitis, iritis and chorioretinitis are common and are found in 30 to 70% of cases. 

They lead to blindness in almost 25% of cases despite treatment.

c- Neurological manifestations

– They are extremely varied and make the disease serious because of the functional after-effects they cause.

– Are dominated by:

Meningoencephalitis. 

Cranial nerve palsies.

The pyramid signs.

Benign intracranial hypertension

Other events:

– Articular : they affect the major joints (knee, ankles), rarely the small joints.

– Cardiac: including myocarditis, endocarditis, rhythm disorders and coronary artery disease.

– Pulmonary : these are essentially infiltrates with or without pleurisy.

– Digestive : dominated by ulcerations and rectocolitis.

– Alteration of general condition (fever at the onset of the illness).

NB: 

Currently, bipolar aphthosis without the systemic manifestations of Behçet’s syndrome, also called “Neumann’s bipolar aphthosis”, is considered a mild form of Behçet’s syndrome.

VII- treatment 

It is necessary to distinguish between symptomatic treatment of aphthae, where the objective is to reduce the pain and duration of the lesion, and treatment of an aphthosis which must be preventive when the flare-ups affect the quality of life. 

In all cases, it is necessary to limit the triggering causes, particularly dietary ones. 

1- Preventive treatment:

• 1.1 Dietary measures:

Hard, crispy, acidic (fruit juice, citrus fruits), salty or spicy (pepper, paprika, chili) foods should be avoided.

Vitamin and mineral supplementation (Vitamins A, D, E, K, B1, B2, B5, B6, B12, C, magnesium, zinc, etc.) 

• 1.2 Oral care:

Restoration of the oral cavity and elimination of local irritant factors.

• 1.3 Hygiene advice:

Regardless of the cause of mouth ulcers, oral hygiene should be promoted by recommending the use of soft-bristled toothbrushes and fluoride toothpaste.

2-Curative treatment

 2.1 Local treatments:

• Most of the products found on the market are local treatments based on hyaluronic acid to promote healing, lidocaine to reduce pain, antiseptic to limit the risk of superinfection or even anti-inflammatories. 
• There are different forms to adapt depending on the patient’s preference and the location of the ulcer: oral gel, spray, mouthwash, lozenges, etc.
• They are used as a first-line treatment.
• Local anesthetics: 

In the form of a gel for isolated forms, or a solution used as a mouthwash for aphthous ulcer, they provide relief to patients during meals but they only have a temporary effect.

Ex: Xylocaine® viscous 2% gel.

• Antiseptics : 

They are mainly intended to prevent bacterial and mycotic superinfections. 

These are mainly mouthwashes based on Chlorhexidine used twice a day. 

 

• Analgesics and non-steroidal anti-inflammatory drugs: 

Ex: 250 to 500 mg of acetylsalicylic acid (1/2 to 1 effervescent aspirin tablet) dissolved in the equivalent of half a glass of water and kept in the mouth, particularly 10 to 15 minutes before a meal [30]. 

• Steroidal anti-inflammatory drugs: 

Ex: – Prednisolone used as a mouthwash 2 to 4 times a day.

      – Hydrocortisone in 2.5 mg lozenge to be left to dissolve on the canker sore [31].

• Use of Amlexanox 5% :

It is a product marketed in the United States under the name Aphtasol®. 

It is an antiallergic and anti-inflammatory, it inhibits the release of inflammatory mediators from neutrophils, basophils and mast cells. It comes in the form of a paste to be applied in small quantities to each canker sore 4 times a day. 

• Antibiotics :

Local antibiotics are widely used, particularly tetracyclines in mouthwash, 2 to 4 times a day (250 mg/5 mL). They are recommended for herpetiform or major aphthosis.

• Use of hyaluronic acid :

Ex: Hyalugel in gel and spray 

Hyaluronic acid 0.2% provides immediate pain relief regardless of the stage of ulceration.

• Physical treatments:

Many physical treatments are used empirically on canker sores. They all aim to cauterize the canker sore, that is, to transform an inflammatory ulceration into a cicatricial ulceration, which is usually less painful. 

We can cite:

• Application of silver nitrate 
• The application of trichloroacetic acid
• Application of protective bioadhesive (carboxymethylcellulose or cyanoacrylate) 
• CO2 laser: remains a current therapy. The application of a few sessions: reduces pain, it does not destroy the cell but it stimulates their defense metabolism, by its analgesic, anti-inflammatory and healing effect. 

2.2 Systemic treatments:

When oral aphthous ulcers are severe, painful and become disabling in daily life, systemic treatment should be considered.

• Colchicine:

It is an anti-gout and anti-inflammatory drug, it works by reducing leukocyte flow.

It is indicated in Behçet’s disease and is used as a preventive treatment against severe outbreaks of aphthous ulcers.

• Thalidomide:

Thalidomide has shown its efficacy in the treatment of severe forms of mouth ulcers in HIV+ patients, and is used for severe flare-ups in immunocompetent patients.

It is used at a dosage of 100 to 200 mg for the treatment of severe ulcers, then increased to 50 mg for maintenance treatment.

In addition, some of its side effects limit its use (sensory neuropathy, teratogenicity, venous thrombosis, drowsiness, digestive discomfort, dry skin, erythematous rash).

• Pentoxifylline : (a drug derived from xanthine).

It inhibits the production of many pro-inflammatory cytokines including TNFα. It has a vasodilatory effect and allows a reduction in the production of fibrinogen.

It is used at a dosage of 400 mg 3 times a day.

• General corticosteroid therapy:

Short-term therapy is advised and gradual dosage reduction is recommended in case of prolonged treatment. 

Oral prednisone at a dosage of 25 mg/day is the treatment of choice in ABR. 

• Azathioprine :

It is an immunosuppressant used in various pathologies: Crohn’s disease, rheumatoid arthritis, lupus erythematosus. 

Used at a dosage of 1 to 2 mg/kg/day, it helps reduce the intensity and severity of orogenital aphthous lesions. 

• Cyclosporine:

It is an immunosuppressant used in the treatment of transplant, nephrotic syndrome and in various autoimmune pathologies. It inhibits the production of pro-inflammatory cytokines.

Used at a dosage of 3 to 6 mg/kg/day, it has proven to be effective for patients with ABR. It can also be combined with corticosteroids. 

Do not use in pregnant women, during breastfeeding and in case of renal insufficiency.

• Vitamin B12 supplementation:

Vitamin B12 deficiency may be the cause of ABR.

Vitamin B12 supplementation may be an effective therapy for ABR, reducing pain, number of ulcers and duration of flare-ups. 

This treatment has the advantage of being inexpensive and without side effects, and it is recommended to use 1 mg of vitamin B12 per day for 6 months.

• Use of Ozone: 

Ozone has interesting properties since it is a powerful oxidant with strong antimicrobial activity.

It increases the oxygen transport capacity of the blood, which allows for more efficient cellular metabolism in tissues with high inflammatory activity.

• Use of natural plant extract: 
• Extracts from Punica Granatum ( pomegranate):

Have antimicrobial activity and antioxidant properties.

• Sesame oil:

Has antimicrobial and anti-inflammatory properties, helping to reduce painful symptoms by accelerating the healing process.

• Ginger:

It is used as an anti-inflammatory and sedative agent.

• Licorice in English. In French, it’s licorice:

Active against bacteria as well as fungal pathogens.

• Aloe Vera:

It has antifungal, anti-inflammatory and immunomodulatory properties. It is able to stimulate the activity of fibroblast growth factor to increase collagen synthesis.

• Conclusion

Although most oral ulcers are trivial lesions, the vigilance and attention of the practitioner should allow the diagnosis of recurrent ulcers and aphthous diseases, a sign of systemic damage indicating an immune deficiency such as HIV.

 • The odontostomatologist will thus be able to treat the patient for minor clinical forms or refer them to specialized hospital services if the condition requires general treatment.

Aphthous ulcer and aphthosis

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Dental implants integrate with the bone for a long-lasting solution.
Yellowed teeth can be brightened with professional whitening.
Dental X-rays reveal problems that are invisible to the naked eye.
Sensitive teeth benefit from specific toothpastes.
A diet low in sugar protects against cavities.
 

Aphthous ulcer and aphthosis