Regardless of the clinical form, ulcers always appear in the same location inside the mouth of the affected individual: the non-keratinized area of the mucosa. Therefore, parts such as tongue dorsum, gums, and hard palate mucosa, all keratinized structures, are never touched by ulceration.

As previously stated, AS tends to affect healthy individuals who are present by no particular clinical condition. The ulcers generally appear during childhood or early adulthood, with 80% of the patients being younger than 30 years, and its frequency and severity tend to decrease with the passing of years. The condition might consist in isolated episodes which usually develop 2-4 times a year, but it might also show a continuous pattern that involves the constant formation of new lesions from older ones soon after healing. Lesions are generally characterized by a disproportionate pain lasting for 4-7 days. The appearance of ulcers is usually preceded by a prodrome of pain and burning which generally lasts for 1-2 days with no previous vesicles. Ulcers present as shallow and well-demarcated bodies with an oval or round shape at the center of which can be seen a yellow-gray pseudo-membrane associated with a red halo and a slightly raised margins of red color.

The most common clinical form is the minor aphthous ulcer which accounts for around 80-85% of cases. The lesions tend to appear on the buccal mucosa and pharynx, on the floor of the mouth or the lateral and ventral positions of the tongue, with a diameter smaller than 1 cm. They heal within 10 days leaving no sign of scarring.

Major aphthous ulcers, on the other hand, represents 10% of the cases of AS and generally sets in after puberty. The main aspect of this form is the tendency of presenting with marked clinical features, with a more intense prodrome and a longer appearance period that usually lasts for several weeks or months. Their size is greater than seen in the minor form, with a diameter generally larger than 1 cm. Major ulcers tend to appear on the soft palate, lips, and throat and might be associated with fever, malaise, dysphagia, and scars.

Lastly, herpetiform aphthous ulcers represent the least common clinical form that accounts for around 5% of the cases of AS. The lesions are much smaller, with a diameter generally ranging between 1 and 3 mm, and they tend to appear in multiple clusters of small and painful ulcers throughout the inside of the month. After a while they tend to coalesce, to turn into lager ulcers which generally disappear after 2 weeks. For this last clinical form a gender-related predisposition has been observed, with lesions more frequently occurring in women than men, usually at a later stage than the one observed in the other forms.

• Anemia

  PURPOSE: To describe a case of atypical, severe, periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA syndrome) in a patient with Fanconi anemia. Important aspects about the PFAPA syndrome and Fanconi anemia are reviewed. [ncbi.nlm.nih.gov]

• Lymphadenopathy

  Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was diagnosed in a 22-year-old man after a 1-year history of periodic fever, myalgia, conjunctivitis, cervical lymphadenopathy, and oral ulcers. [ncbi.nlm.nih.gov]

  Complex aphthosis is also seen in rarer conditions such as MAGIC syndrome (mouth and genital ulcers, inflamed cartilage), PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and lymphadenopathy), and cyclical neutropenia (fever approximately [visualdx.com]

  In severe cases, other symptoms of Sutton disease II may include a general feeling of weakness (malaise), fever, and swollen lymph nodes around the neck and head (lymphadenopathy). Causes The exact cause of Sutton disease II is not known. [rarediseases.org]

• Localized Pain

  Topical anesthetics such as lidocaine are frequently prescribed for local pain relief. Troublesome ulcers may be treated with a topical corticosteroid in a paste, cream, spray, or rinse. [ibdcrohns.about.com]

  These vesicles may rupture and cause tremendous local pain. Aphthous stomatisis, on the other hand, is caused by factors other than viral infection – as already explained. [hxbenefit.com]

  Over-the-counter agents such as Orabase or Zilactin-B coat aphthous ulcers and provide local protection. 11 Brief anesthesia may be obtained with the application of a silver nitrate stick, although the application itself is quite painful. [aafp.org]

• Aphthous Stomatitis

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

  OBJECTIVES: The aetiology of recurrent aphthous stomatitis remains unknown. [ncbi.nlm.nih.gov]

  Vitamin B12 for aphthous stomatitis Vitamin B12 is a safe, effective, and inexpensive treatment for recurrent aphthous stomatitis. Dr. [raysahelian.com]

  Recurrent aphthous stomatitis (RAS) affects 20 to 30% of adults and a greater percentage of children at some time in their life. Etiology is unclear, but recurrent aphthous stomatitis (RAS) tends to run in families. [msdmanuals.com]

  The clinical appearance and histopathologic features of the ulcers were consistent with aphthous stomatitis. [cmaj.ca]

• Aphthous Ulceration

  Aphthous ulcers, or canker sores, are the most common recurrent oral ulcers in the U.S. There are three subtypes: minor, major, and herpetiform, with minor aphthous being the most commonly reported form. [dentalcare.com]

  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. [standardofcare.com]

  Figure 1 (a) Minor-type oral aphthous ulcers, (b) major-type oral aphthous ulcer, (c) herpetiform oral aphthous ulcers Another classification is based on the time course. [aerzteblatt.de]

  Ulcer, Aphthous is a topic covered in the 5-Minute Clinical Consult. [unboundmedicine.com]

  Recurrent aphthous ulcers may also accompany malignancy or autoimmune disease. [aneskey.com]

• Oral Ulcers

  Aphthous ulcers, or canker sores, are the most common recurrent oral ulcers in the U.S. There are three subtypes: minor, major, and herpetiform, with minor aphthous being the most commonly reported form. [dentalcare.com]

  […] tend to occur less often than oral ulcers. [musculoskeletalkey.com]

  The index evaluated the oral ulcer activity, ulcer-related pain, and functional disability. Oral ulcer activity was recorded as number of ulcers in the past 1 month. [ncbi.nlm.nih.gov]

• Recurrent Oral Ulceration

  Aphthous ulcers, or canker sores, are the most common recurrent oral ulcers in the U.S. There are three subtypes: minor, major, and herpetiform, with minor aphthous being the most commonly reported form. [dentalcare.com]

  HLA-A, B, C na DR Antigens in Recurrent Oral Ulcers. Ann Dent. 1988;47(1):5-8. [ Links ] 15. Sistig S, Cekic-Arambasin A, Rabatic S, Vucicevic-Boras V, Kleinheinz J, Piffko J. Natural immunity in recurrent aphthous ulceration. [scielo.br]

  Recurrent oral ulceration Minor aphthous, major aphthous, or herpetiform ulceration observed by physician or patient recurring at least three times in one 12-month period Plus two of: Recurrent genital ulceration Aphthous ulceration or scarring, observed [musculoskeletalkey.com]

  Abstract Recurrent oral ulceration is common and may present in childhood. Causes of recurrent oral ulceration are numerous and there may be an association with underlying systemic disease. [magonlinelibrary.com]

  Hypofunction of the sympathetic nervous system should be considered as a possible etiologic factor in patients with recurrent oral ulcers when not associated with known systemic diseases. [ncbi.nlm.nih.gov]

• Sore Mouth

  Photo by quayside/Bigstockphoto.com Cold sores are outside the mouth. Canker sores are inside the mouth. Canker sores, aka mouth ulcers, are not the same as cold sores. [saidsupport.org]

  […] tissues of the mouth. [epainassist.com]

  (sore) K12.0 Periadenitis mucosa necrotica recurrens K12.0 Sore mouth K13.79 ICD-10-CM Diagnosis Code K13.79 Other lesions of oral mucosa 2016 2017 2018 2019 Billable/Specific Code Applicable To Focal oral mucinosis canker K12.0 Stomatitis (denture) [icd10data.com]

• Papule

  Ulcers may be preceded by papules or pustules, and morphologically their appearance is similar to oral aphthae with round and sharp erythematous border (punched-out), covered with grayish-white pseudomembrane or central yellowish fibrinous base; they [musculoskeletalkey.com]

  Hand-foot-and-mouth disease · Ulcers preceded by vesicles · Skin lesions, low-grade fever, and malaise Erythema multiforme · Lesions on attacthed and unattached mucosa; lip crusting · May be preceded by herpes infection · Sudden onset of skin macules and papules [mah.se]

  Sweet syndrome, in which mouth ulcers are found with conjunctivitis, episcleritis and inflamed tender skin papules or nodules. Drug use, especially NSAIDs and nicorandil. [pocketdentistry.com]

  Within two days, a raised erythematous (red) papule or white spot appears. This ulcerates, resulting in a pseudomembranous grayish or yellowish center within the lesion. Minor aphthae are round or oval and measure up to 4 mm in diameter. [dentalacademyofce.com]

• Skin Papule

  Sweet syndrome, in which mouth ulcers are found with conjunctivitis, episcleritis and inflamed tender skin papules or nodules. Drug use, especially NSAIDs and nicorandil. [pocketdentistry.com]

The diagnosis of AS can generally be performed by using the following laboratory studies:

• Complete blood cell count, usually employed to determine hemoglobin concentration and the levels of glucose-6-phosphate dehydrogenase and glycemia. 
• Measurement of the levels of iron, folate, ferritin, and vitamins B-6 and B-12 [8]
• Measurement of erythrocyte sedimentation rate
• Laboratory tests like Tzanck test, viral culture, or skin biopsy. These tests are necessary to rule out the presence of simplex virus infection, especially in immunocompromised individuals diagnosed with HIV. 

Because of the lack of definitive histological features and tests, diagnosis is invariably made by an exclusion process based on the clinical history and lesion presentation [9].

• Helicobacter Pylori

  Epidemiology of Helicobacter pylori infection. Helicobacter 2007;12:1-3. 21. Makola D, Peura DA, Crowe SE. Helicobacter pylori infection and related gastrointestinal diseases. J Clin Gastroenterol 2007;41:548-58. 22. [ijds.in]

  Helicobacter pylori (H. pylori) is a gram-negative, microaerophile bacteria, that colonizes the gastric mucosa and it was previously suggested to be involved in RAS development. [ncbi.nlm.nih.gov]

  The effect of gastric Helicobacter pylori eradication on recurrent aphthous stomatitis. Int J Dermatol 2008; 47 : 615–617. [nature.com]

  pylori infection Epstein-Barr virus ( 1 ) -- To view the remaining sections of this topic, please sign in or purchase a subscription -- TY - ELEC T1 - Ulcer, Aphthous ID - 117080 ED - Baldor,Robert A, ED - Domino,Frank J, ED - Golding,Jeremy, ED - Stephens [unboundmedicine.com]

There is a variety of agents that are used to treat recurrent aphthous ulcers. These range from agents with palliative effects to those which shorten the healing time [10] [11] and prevent recurrence. Topical agents include:

• Anti-inflammatory and immunomodulatory agents: These are used immediately, at the beginning of the treatment, and generally include a variety of different products such as topical gels, creams, ointments, and sprays. 
• Adjuvant rinses: These have proven to reduce the presence of pathogens inside the mouth, and are thought to lower inflammatory levels and healing time. The most important products include chlorhexidine gluconate and diluted hydrogen peroxide.
• Oral bioadherents: They are generally used to reduce pain, which sometimes might be very severe and disproportionate compared to the size of lesions. The mucoadhesives form a protective coating which alleviates pain. 

Systemic agents include:

• Colchicine: This medication is commonly used to treat gout and was originally extracted from the plants of the genus Colchicum.
• Prednisone: This is a corticosteroid used as an alternative for Colchicine. 
• Azathioprine: This is an immunosuppressive drug used in organ transplantation and autoimmune diseases.
• Montelukast sodium: This is an active leukotriene receptor antagonist which has been reported having few adverse effects, especially when compared to steroids [12]. 
• Thalidomide: This is an immunomodulatory drug especially used to treat individuals affected by HIV infection. 
• Clofazimine: This is a fat-soluble iminophenazine dye used in multidrug therapy to treat leprosy. This drug is especially indicated in those showing the tendency of continuously experiencing the appearance of new lesions [13].

There is no surgical approach to treat recurrent aphthous ulcers [14]. Diet modifications are strongly suggested, as outbreaks of AS might be caused by allergic stimuli whose frequency can be drastically reduced, for not saying eliminated at all, with finely chosen food changes [15] [16] [17].

The mainstay for the treatment for AS is undoubtedly represented by the use of chlorhexidine gluconate mouthwashes and topical corticosteroids. These should be applied during prodrome, so that clinical signs can be reduced before their development. The corticosteroid dexamethasone 0.5 mg/5 mL is particularly effective in rinses, generally followed by the use of ointments like clobetasol ointment 0.05% or fluocinonide ointment 0.05% in mucosal protective paste. If topical corticosteroids turn out to be ineffective to treat ulcers, they may be replaced by prednisone which is usually administered in doses of 40 mg once a day in a 5 days treatment. Severe cases are best treated with systemic corticosteroids and immunosuppressants. Some agents can even be administered intralesionally, especially with betamethasone, dexamethasone, or triamcinolone.

AS frequently tends to appear in healthy individuals, with no particular clinical consequences. However, in some cases it might be associated with a systemic disease like Behcet's syndrome or inflammatory bowel disease, in a clinical situation which might easily result into a significant morbidity or mortality.

Unfortunately, despite the clear clinical characterization that has been defined over the course of the years, the etiology of AS is still unknown, and no precise cause responsible for its appearance can be suggested. However, the most commonly accepted theory among experts is that AS must be a multifactorial condition which originates from immune-related events that cause the self-destruction of the oral epithelium. The destruction is mostly cell-mediated, with the intervention of cytokines like IL-2, IL-10, and in particular TNF-α, all well known inflammatory mediators playing a pivotal role in the functioning of the immune system.

Of note, many individuals affected by AS show hematinic deficiencies, especially in terms of low levels of iron, folic acid, and vitamins B-6 and B-12 [1], which appear twice as frequently as in healthy individuals. Furthermore, the pathological condition seems to run in certain families, as suggested by the high appearance frequency in identical twins [2], and this tendency might underline the involvements of genetic factors in the etiology of AS.

In America, AS appears to affect around 20% of the population, even though it seems to be particularly frequent in certain social groups, such as the students of professional schools. Strangely enough, the condition is more common among children with a high socioeconomic background [6]. Internationally, AP affects all populations in every continent, with an international frequency that ranges from 2 to 66% according to the particular country considered [3]. There is no evident gender-related predisposition, even though in particular social groups the pathology might be much more common in females than males. In America, around 1% of the children can be affected by recurrent AS, with an early onset which generally appears before the age of 5 years. The percentage of affected individuals tends to decrease after reaching the age of 30. In other individuals, the onset of AS might take place after puberty and generally tends to persist for the rest of their life, although less frequently. To sum up, AP primarily affects young individuals, but its incidence and severity tends to decrease over the years [4] [5] [6] [7].

Thanks to the clinical data gathered so far, it is now possible to categorize aphthous ulcers into three main clinical forms: recurrent aphthous ulcer minor, recurrent aphthous ulcer major, and herpetiform recurrent aphthous ulcer.

The most common of these forms is recurrent aphthous ulcer minor, which appears as a discrete, shallow, and painful lesion usually smaller than 1 cm in diameter. There might be just one minor ulcer present in the mouth at a time, but frequently more than one is observed. This clinical form accounts for more than 80% of the AS cases.

Recurrent aphthous ulcer major, on the other hand, is much less common than the minor form. It presents in an oval shape and its diameter is usually greater than 1 cm. In this form, there might be many lesions in the mouth at a time. These are large and deep ulcers with irregular borders that may coalesce after a while.

Herpetiform recurrent aphthous ulcer is the least common form, with a frequency of around 5-10%. It is characterized by a reduced size that is usually no larger than 1 mm in diameter. For this reason, sometimes it is possible to observe the appearance of this clinical form with the development of tiny ulcers in clusters of tens or hundreds of units which might be localized in certain points or be spread throughout the oral soft mucosa.

Outbreak of aphthae might be prevented with a gluten-free diet in celiac patients. Those who already have lesions in their mouth are advised to avoid hard and sharp foods, to prevent worsening the conditions of the already existing ulcers or the formation of new ones. Furthermore, affected individuals should also evade salt and hot spices, which might increase the already severe pain that  characterizes AS. In this regards, it is worth noting that the appearance of aphthae has been reported after the ingestion of cinnamon, nuts, and pineapples, which might act as inciting agents.

According to some studies, there is an association between smoking and the occurrence of AS, which might be reduced by using tobacco. For example, the incidence of recurrent aphthous ulcer is significantly lower in smoking people than the incidence observed in non smokers [18] [19]. This tendency is explained with the capacity of tobacco to increase keratinization in the mucosa, which as a consequence might remain much less exposed to ulceration. In other words, nicotine that is locally absorbed, might work as a preventing agent against the formation of lesions.

Aphthous stomatitis (AS) is also referred to as recurrent aphthous ulcers (RAU) or canker sores. This type of ulceration represents one of the most common mucosal lesions, usually found even in healthy individuals affected by no other pathological condition. Although AS is characterized by a clinically significant morbidity, its etiology remains generally unknown. The lesions consist of ulcers which appear on the mucous membranes inside the oral cavity for 7 to 10 days. Some lesions might even last for several weeks, leaving scars after the completion of the healing process.

Generally speaking, the activity for idiopathic recurrent aphthous ulcers is self-limiting, but in some cases it might appear as a continuous process. Furthermore, similar lesions can be seen in the genital region. As previously stated, AS frequently affects healthy individuals, even though in some cases it might be associated with other pathological conditions such as Behcet's syndrome or systemic lupus erythematosus.

Aphthous stomatitis (canker sores, or aphthous ulcers) is a pathological condition characterized by the presence of small and painful ulcers inside the mouth which usually appears in childhood and tends to recur over the course of the years. This condition is common, but its origin is still unknown, even though it tends to run in families. However, many experts believe that this is a multifactorial pathology which might be favored or triggered by several factors such as oral injuries, stress and certain foods. Symptoms include pain and burning in the initial stage, that is then followed by a ulcer after a few days. Pain is disproportionally severe and usually lasts from 4 to 7 days. The lesions present as soft and loose formations, usually less than 1 cm in diameter, and frequently gather in clusters of two or more units. Ulcers tend to disappear by themselves within 7-10 days leaving no scar on the oral tissue affected. Treatment is palliative and based on general measures such as the use of corticosteroid combined with frequent rinses.

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