Aphthous Stomatitis (Aphthae)

Aphtha2[1]

Aphthous stomatitis is a pathological condition which consists in the appearance of benign and non-contagious ulcers in the oral cavity.

Aphthous Stomatitis originates from this process: infectious.

Presentation

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.

Entire body system
Reiter's Syndrome
  • Uveitis or iritis may be present with Reiter syndrome or Behçet syndrome.[oralmaxillo-facialsurgery.blogspot.com]
  • Non-oral symptoms of Behçet's syndrome may be present in 43 to 100 percent of patients with recurrent aphthous ulcers, depending on severity. 6 Reiter's syndrome is associated with oral ulcers, uveitis, conjunctivitis and HLA B27-positive arthritis following[aafp.org]
  • ., Reiter syndrome), and HIV/AIDS.[oasisdiscussions.ca]
  • Seems like reiters syndrome will fUse many of the same...[thebody.com]
  • HIV) Autoimmune disorder: Behcet's syndrome Reiter's syndrome Inflammatory bowel disease Systemic lupus erthematosus Celiac disease Recurrences more than 6 times yearly History of ulcers that last 14 days, or heal with scarring Systemic symptoms (fever[medsask.usask.ca]
Relapsing Polychondritis
  • 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.[standardofcare.com]
  • O’Duffy Mouth and genital ulcers with inflamed cartilage: MAGIC syndrome, Five patients with features of relapsing polychondritis and Behçet's disease Am J Med, 79 (1985), pp. 65-72 55 S.R.[reumatologiaclinica.org]
  • The name stands for "mouth and genital ulcers with inflamed cartilage" ( relapsing polychondritis ). [8] PFAPA syndrome is a rare condition that tends to occur in children. [8] The name stands for "periodic fever , aphthae, pharyngitis (sore throat) and[en.wikipedia.org]
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  • Jaw & Teeth
    Aphthous Stomatitis
    • Aphthous Stomatitis Prognosis Minor recurrent aphthous stomatitis and herpetiform ulcer seem to be limited over a certain period of time.[hxbenefit.com]
    • Canker sores, or aphthous ulcers, are the lesions caused by aphthous stomatitis.[ibdcrohns.about.com]
    • aphthous stomatitis in Medicine aphthous stomatitis n.[dictionary.reference.com]
    Tongue Ulcer
    • Symptoms include: Painful ulcers in the mouth, usually inside the lips, on the cheeks, or on the tongue Ulcers that are covered with a yellow layer and have a red base No fever present (in most cases) Lesions usually heal in seven to 14 days Lesion tend[cincinnatichildrens.org]
    • Signs and symptoms may include: Ulcers in the mouth, usually inside the lips, on the cheeks, or on the tongue Ulcers that are covered with a yellow layer and have a red base No fever present (in most cases) Lesions usually heal in seven to 14 days Lesions[chop.edu]
    • Symptoms may include: Ulcers in the mouth, usually inside the lips, on the cheeks, or on the tongue Ulcers that are covered with a yellow layer and have a red base No fever present (in most cases) Lesions usually heal in seven to 14 days Lesions tend[nyhq.org]
    • […] stomatitis (major) (minor) Bednar's aphthae Periadenitis mucosa necrotica recurrens Recurrent aphthous ulcer Stomatitis herpetiformis cachectic K14.0 ICD-10-CM Diagnosis Code K14.0 Glossitis 2016 2017 2018 Billable/Specific Code Applicable To Abscess of tongue[icd10data.com]
    Sore Mouth
    • Mouth Ulcer Treatment Aphthous stomatitis, aka mouth ulcers, can be very painful.[saidsupport.org]
    • Also known as "canker sores," mouth ulcers are shallow sores found on the inner cheeks, lips, or gums.[pharmacytimes.com]
    • : No change Aphthae, aphthous - see also condition ulcer (oral) (recurrent) K12.0 Bednar's K12.0 oral K12.0 (recurrent) stomatitis K12.0 (major) (minor) Bednar's aphthae K12.0 Canker (mouth) (sore) K12.0 Periadenitis mucosa necrotica recurrens K12.0 Sore[icd10data.com]
    • Mouth rinses, which have the steroid dexamethasone, are prescribed for multiple canker sores.[epainassist.com]
    • Called also chronic atrophic candidiasis and denture sore mouth . gangrenous stomatitis see noma . herpetic stomatitis herpes simplex involving the oral mucosa and lips, characterized by the formation of yellowish vesicles that rupture and produce ragged[medical-dictionary.thefreedictionary.com]
    Lesion of the Tongue
    • If there are lesions on the tongue, speaking and chewing can be uncomfortable.[nursingcenter.com]
    • Pain is worst in the days immediately following the initial formation of the ulcer, and then recedes as healing progresses. [3] If there are lesions on the tongue, speaking and chewing can be uncomfortable, and ulcers on the soft palate , back of the[en.wikipedia.org]
    Hypersalivation
    • Acrodynia (Pink disease): Oral and perioral ulceration, hypersalivation, gingivitis and early tooth loss are features of acrodynia caused by mercury poisoning, now rarely seen.[stmina-monastery.org]
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  • Workup

    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].

    Laboratory

    Microbiology
    Helicobacter Pylori
    • Diagnostik Labor Mikrobiologie Helicobacter pylori pylori DNA in recurrent aphthous stomatitis tissue by PCR - MP Riggio, A Lennon, D Wray - Journal of oral pathology & , 2002 - Wiley Online Library Association between Helicobacter pylori and recurrent[symptoma.com]
    • ., menstrual cycle) ( 2 ) Helicobacter pylori infection Epstein-Barr virus ( 1 ) -- To view the remaining sections of this topic, please sign in or purchase a subscription --[unboundmedicine.com]
    • Detection of Helicobacter pylori in oral aphthous ulcers.[emedicine.medscape.com]
    Human Herpesvirus 6
    • Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis .[immunoloji.uludag.edu.tr]
    • Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis.[emedicine.medscape.com]
    • Bagg Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis J Oral Pathol Med, 28 (1999), pp. 12-15 20 D.[reumatologiaclinica.org]
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  • Treatment

    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.

    Prognosis

    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.

    Complications

    Aphthous Stomatitis
    • Aphthous Stomatitis Prognosis Minor recurrent aphthous stomatitis and herpetiform ulcer seem to be limited over a certain period of time.[hxbenefit.com]
    • Canker sores, or aphthous ulcers, are the lesions caused by aphthous stomatitis.[ibdcrohns.about.com]
    • aphthous stomatitis in Medicine aphthous stomatitis n.[dictionary.reference.com]
    Erythema Multiforme
    • multiforme · Lesions on attacthed and unattached mucosa; lip crusting · May be preceded by herpes infection · Sudden onset of skin macules and papules · Target lesions on skin Oral lichen planus · Erosive and reticular lesions on buccal mucosa, gingiva[mah.se]
    • 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.[standardofcare.com]
    • Other causes of mouth ulcer should be considered, including: Herpes simplex Herpangina Erythema multiforme Fixed drug eruption .[dermnetnz.org]
    Stomatitis
    • Aphthous stomatitis is not contagious.[encyclopedia.com]
    • […] oraal , orale aften , afte , orale aftoïde ulcus , zweren aftoïd oraal , stomatitis aftoïd , aftoïde stomatitis , aften; oraal , aften; stomatitis , aften; ulcus , aphthosa; stomatitis , aphthosum; ulcus , oraal; aften , stomatitis; aften , stomatitis[fpnotebook.com]
    • Synonym(s): aphthae minor , aphthous stomatitis , canker sores , recurrent aphthous stomatitis , recurrent aphthous ulcers , recurrent ulcerative stomatitis , ulcerative stomatitis .[medical-dictionary.thefreedictionary.com]
    • (denture) (ulcerative) K12.1 ICD-10-CM Diagnosis Code K12.1 Other forms of stomatitis 2016 2017 2018 Billable/Specific Code Applicable To Stomatitis NOS Denture stomatitis Ulcerative stomatitis Vesicular stomatitis Type 1 Excludes acute necrotizing ulcerative[icd10data.com]
    Ulcerative Colitis
    • Gastrointestinal disease: pernicious anaemia, coeliac disease and dermatitis herpetiformis (rare in DH), Crohn's disease and ulcerative colitis.[stmina-monastery.org]
    • Crohn’s disease and ulcerative colitis may also be accompanied by oral ulcers.[freysmiles.com]
    • colitis Behcet's disease, a rare disorder that causes inflammation throughout the body, including the mouth A faulty immune system that attacks healthy cells in your mouth instead of pathogens, such as viruses and bacteria HIV/AIDS, which suppresses[mayoclinic.org]
    • colitis HIV infection Behcet syndrome Canker sores can be various sizes.[health.cvs.com]
    Crohn's Disease
    • Significant oral involvement occurs in 10 to 15% of patients with Crohn’s disease, usually in people at the severe end of the spectrum of Crohn’s disease.[medicinetoday.com.au]
    • Certain blood diseases, vitamin and mineral deficiencies, allergies, trauma and Crohn's disease cause similar ulcers.[colgateprofessional.com]
    Vitamin B12 Deficiency
    • Approaches to vitamin B12 deficiency.[ispub.com]
    • B12 deficiency, malabsorption, celiac disease , regional enteropathy, menstruation, food hypersensitivity (eg, cow's milk), 8 allergic reaction, and exposure to toxins (eg, nitrates in drinking water).[oralmaxillo-facialsurgery.blogspot.com]
    • Although these studies found that 0–42% of those with recurrent ulcers suffer from vitamin B12 deficiency, an association with deficiency is rare.[en.wikipedia.org]
    Acquired Immunodeficiency Syndrome
    • Consider Behçet disease; human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); cancer; Crohn disease ; immunocompromised state; cyclic neutropenia; mouth and genital ulcers with inflamed cartilage (MAGIC syndrome);[oralmaxillo-facialsurgery.blogspot.com]
    Reiter's Syndrome
    • Uveitis or iritis may be present with Reiter syndrome or Behçet syndrome.[oralmaxillo-facialsurgery.blogspot.com]
    • Non-oral symptoms of Behçet's syndrome may be present in 43 to 100 percent of patients with recurrent aphthous ulcers, depending on severity. 6 Reiter's syndrome is associated with oral ulcers, uveitis, conjunctivitis and HLA B27-positive arthritis following[aafp.org]
    • ., Reiter syndrome), and HIV/AIDS.[oasisdiscussions.ca]
    • Seems like reiters syndrome will fUse many of the same...[thebody.com]
    • HIV) Autoimmune disorder: Behcet's syndrome Reiter's syndrome Inflammatory bowel disease Systemic lupus erthematosus Celiac disease Recurrences more than 6 times yearly History of ulcers that last 14 days, or heal with scarring Systemic symptoms (fever[medsask.usask.ca]
    Systemic Lupus Erythematosus
    • Recurrent multiple ulcers, especially in the absence of concomitant genital ulcers, are most typical (but not limited) of the following conditions: recurrent aphthous stomatitis (RAS), systemic lupus erythematosus (SLE), inflammatory bowel disease, celiac[musculoskeletalkey.com]
    • lupus erythematosus - typical butterfly rash, usually painless oral ulcers Celiac disease - history of intolerance to gluten Squamous cell carcinoma - if ulcers persist without healing.[medsask.usask.ca]
    • RAS must be distinguished from other diseases that cause recurring oral ulcers such as Behcet's syndrome, systemic lupus erythematosus, celiac disease, and Crohn's disease 6 .[immunoloji.uludag.edu.tr]
    • Rothfield The 1982 revised criteria for the classification of systemic lupus erythematosus Arthritis Rheum, 25 (1982), pp. 1271-1277 44 Criteria for diagnosis of Behçet's disease.[reumatologiaclinica.org]
    Behçet Disease
    • International Study Group for Behçet’s Disease: Criteria for diagnosis of Behçet’s disease.[aerzteblatt.de]
    • Behçet Disease in a Child—Emphasis on Cutaneous Manifestations.[journals.cambridge.org]
    • Aetiology of RAS: Behçet's disease .[stmina-monastery.org]
    • Anti-TNF agents for Behçet's disease: análisis of publisher data on 369 patients.[reumatologiaclinica.org]
    • 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.[standardofcare.com]
    Celiac Disease
    • View Article PubMed Google Scholar Catassi C: [The global village of celiac disease].[bmcgastroenterol.biomedcentral.com]
    • Screening for celiac disease may also need to be ruled out.[oasisdiscussions.ca]
    • […] than 5% of people with RAS have Celiac disease, which usually presents with severe malnutrition, anemia, abdominal pain , diarrhea and glossitis (inflammation of the tongue). [8] Sometimes aphthous-like ulcerations can be the only sign of celiac disease[en.wikipedia.org]
    • Some cases of complex canker sores are caused by an underlying health condition, such as an impaired immune system; nutritional problems, such as vitamin B-12, zinc, folic acid , or iron deficiency ; or gastrointestinal tract disease, such as celiac disease[m.webmd.com]
    Tongue Ulcer
    • Symptoms include: Painful ulcers in the mouth, usually inside the lips, on the cheeks, or on the tongue Ulcers that are covered with a yellow layer and have a red base No fever present (in most cases) Lesions usually heal in seven to 14 days Lesion tend[cincinnatichildrens.org]
    • Signs and symptoms may include: Ulcers in the mouth, usually inside the lips, on the cheeks, or on the tongue Ulcers that are covered with a yellow layer and have a red base No fever present (in most cases) Lesions usually heal in seven to 14 days Lesions[chop.edu]
    • Symptoms may include: Ulcers in the mouth, usually inside the lips, on the cheeks, or on the tongue Ulcers that are covered with a yellow layer and have a red base No fever present (in most cases) Lesions usually heal in seven to 14 days Lesions tend[nyhq.org]
    • […] stomatitis (major) (minor) Bednar's aphthae Periadenitis mucosa necrotica recurrens Recurrent aphthous ulcer Stomatitis herpetiformis cachectic K14.0 ICD-10-CM Diagnosis Code K14.0 Glossitis 2016 2017 2018 Billable/Specific Code Applicable To Abscess of tongue[icd10data.com]
    Wegener Granulomatosis
    • Wegener's granulomatosis Cytotoxic agents as methotrexate Irradiation of oral mucosa There are three main clinical types of RAS: Minor aphthous ulcers Major aphthous ulcers Herpetiform ulceration Age of onset Childhood or adolescence Childhood or adolescence[stmina-monastery.org]
    • Wegener's granulomatosis: oral or nasal inflammation to the development of painful or painless oral ulcers or purulent or bloody nasal discharge. 45 4.[reumatologiaclinica.org]
    Relapsing Polychondritis
    • 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.[standardofcare.com]
    • O’Duffy Mouth and genital ulcers with inflamed cartilage: MAGIC syndrome, Five patients with features of relapsing polychondritis and Behçet's disease Am J Med, 79 (1985), pp. 65-72 55 S.R.[reumatologiaclinica.org]
    • The name stands for "mouth and genital ulcers with inflamed cartilage" ( relapsing polychondritis ). [8] PFAPA syndrome is a rare condition that tends to occur in children. [8] The name stands for "periodic fever , aphthae, pharyngitis (sore throat) and[en.wikipedia.org]
    Pemphigus
    • […] tongue · White (Wickham's) striae · May be asymptomatic · Lesions may occur on skin Cicatricial pemphigoid · Vesiculobullous lesions on attached and unattached mucosa · Positive Nikolsky's sign · Can affect eyes and genitalia · Lesions can occur on skin Pemphigus[mah.se]
    • Lupus erythematosus, bullous pemphigoid and pemphigus vulgaris are other diseases that may involve ulceration of the mouth.[aafp.org]
    • Ulcers may appear as single or multiple lesions, and they are easily distinguished from primary or secondary viral infections, bacterial infections (eg, necrotizing ulcerative gingivitis), dermatologic conditions (lichen planus, cicatricial pemphigoid, pemphigus[oralmaxillo-facialsurgery.blogspot.com]
    • Pemphigus Erosions Erosions Multiple flaccid bullae 6.[stmina-monastery.org]
    Herpes Labialis
    • Objectives Prevention Adult Caries Root Caries Gingivitis Periodontitis Tooth Changes with Aging Tooth Loss Oral Effects of Medications Gingival Hyperplasia Dental Erosions Xerostomia Alcohol & Tobacco Meth Mouth Common Oral Lesions Chapter Objectives Herpes[smilesforlifeoralhealth.org]
    • The patient with recurrent aphthous ulcers and the patient with recurrent herpes labialis: A study of two population samples.[dovemed.com]
    • ., and the wavelength of these diode lasers ranges from 630 to 910 nm. [7] , [11] In addition to its role in the management of RAS, it has a wide spectrum of clinical applications which include herpes labialis, angular cheilitis, trismus, paresthesia,[jofs.in]
    • Clinical effectiveness of lysine in treating recurrent aphthous ulcers and herpes labialis.[emedicine.medscape.com]
    Hand, Foot and Mouth Disease
    • […] vesicles Varicella zoster virus · Extraoral and intraoral ulcers · Unilateral distribution · Prodrome of pain and burning · May cause scarring and neuralgia Herpangina · Multiple ulcers in hard palate, soft palate, and oropharynx · Fever and malaise Hand-foot-and-mouth[mah.se]
    • Mouth ulcers can be caused by other conditions (such as contact dermatitis , herpes infection , hand-foot-and-mouth disease , and lupus) that may need treatment so they should always be seen by a physician for a diagnosis.[ibdcrohns.about.com]
    • Herpangina and hand-foot-and-mouth disease can produce ulcers resembling aphthous ulcers, but these ulcers are instead part of Coxsackie viral exanthems, usually occurring with fever and in clusters among children.[aneskey.com]
    • Oculomucocutaneous syndromes: (see table above) Other causes: (see table below) Other causes of oral ulcers Viral infections: Herpes simplex stomatitis, chickenpox and herpes zoster, hand, foot and mouth disease, herpangina (Coxsackie viruses), infectious[stmina-monastery.org]
    • Skin findings should be normal, but rash may be present with Behçet syndrome, erythema multiforme, hand-foot-and-mouth disease, herpes simplex infection, lichen planus, MAGIC syndrome, pemphigus, pemphigoid, Sweet syndrome, syphilis, systemic lupus erythematosus[oralmaxillo-facialsurgery.blogspot.com]
    Lichen Planus
    • Burning Mouth Syndrome - NIH (National Institute of Dental and Craniofacial Research) Drooling (Medical Encyclopedia) Gum biopsy (Medical Encyclopedia) Herpangina (Medical Encyclopedia) Leukoplakia (Medical Encyclopedia) Lichen planus (Medical Encyclopedia[icdlist.com]
    • planus · Erosive and reticular lesions on buccal mucosa, gingiva, palate, and tongue · White (Wickham's) striae · May be asymptomatic · Lesions may occur on skin Cicatricial pemphigoid · Vesiculobullous lesions on attached and unattached mucosa · Positive[mah.se]
    • Planus Leukoplakia & Erythoplakia Oral Cancer Oral Cancer:Treatment Denture Problems Prophylaxis & Anticoagulation Chapter Objectives Coordination of Care Endocarditis Prophylaxis Conditions Procedures Dosing Implanted Devices Managing Anticoagulation[smilesforlifeoralhealth.org]
    • planus or herpes simplex Treating Mouth Ulcers Treatment of RAS typically is palliative, although supplementing the diet with lysine or the aforementioned nutrients may work as a preventive measure.[pharmacytimes.com]
    Bullous Pemphigoid
    • Lupus erythematosus, bullous pemphigoid and pemphigus vulgaris are other diseases that may involve ulceration of the mouth.[aafp.org]
    • Autoimmune disease: Behcet's syndrome, Reiter's syndrome, inflammatory bowel disease, lupus erythematosus, bullous pemphigoid, and pemphigus vulgaris.[dentalresource.org]

    Etiology

    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.

    Causes

    Acquired Immunodeficiency Syndrome
    • Consider Behçet disease; human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); cancer; Crohn disease ; immunocompromised state; cyclic neutropenia; mouth and genital ulcers with inflamed cartilage (MAGIC syndrome);[oralmaxillo-facialsurgery.blogspot.com]
    Celiac Disease
    • View Article PubMed Google Scholar Catassi C: [The global village of celiac disease].[bmcgastroenterol.biomedcentral.com]
    • Screening for celiac disease may also need to be ruled out.[oasisdiscussions.ca]
    • […] than 5% of people with RAS have Celiac disease, which usually presents with severe malnutrition, anemia, abdominal pain , diarrhea and glossitis (inflammation of the tongue). [8] Sometimes aphthous-like ulcerations can be the only sign of celiac disease[en.wikipedia.org]
    • Some cases of complex canker sores are caused by an underlying health condition, such as an impaired immune system; nutritional problems, such as vitamin B-12, zinc, folic acid , or iron deficiency ; or gastrointestinal tract disease, such as celiac disease[m.webmd.com]

    Epidemiology

    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].

    Sex distribution
    Age distribution

    Pathophysiology

    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.

    Prevention

    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.

    Summary

    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.

    Patient Information

    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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    Marshall's Syndrome
    • Update on treatment of Marshall’s syndrome (PFAPA syndrome): Report of five cases with review of the literature.[acep.org]
    • Update on treatment of Marshall’s syndrome (PFAPA syndrome): report of five cases with review of the literature.[journals.lww.com]
    • Update on treatment of Marshall's syndrome (PFAPA syndrome): report of five cases with review of the literature.[immunoloji.uludag.edu.tr]

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    References

    1. Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med. 2010 Feb 7.
    2. Miller MF, Garfunkel AA, Ram C, Ship II. Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol. 1977 Jun. 43(6):886-91.
    3. Axéll T, Henricsson V. The occurrence of recurrent aphthous ulcers in an adult Swedish population. Acta Odontol Scand. 1985 May. 43(2):121-5.
    4. Vincent SD, Lilly GE. Clinical, historic, and therapeutic features of aphthous stomatitis. Literature review and open clinical trial employing steroids. Oral Surg Oral Med Oral Pathol. 1992 Jul;74(1):79-86.
    5. Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, Häyrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg. 2004 Apr;33(3):221-34.
    6. Kleinman DV, Swango PA, Niessen LC. Epidemiologic studies of oral mucosal conditions--methodologic issues. Community Dent Oral Epidemiol. 1991 Jun;19(3):129-40.
    7. Reichart PA. Oral mucosal lesions in a representative cross-sectional study ofaging Germans. Community Dent Oral Epidemiol. 2000 Oct;28(5):390-8.
    8. Rogers RS 3rd, Hutton KP. Screening for haematinic deficiencies in patients with recurrent aphthous stomatitis. Australas J Dermatol. 1986 Dec. 27(3):98-103.
    9. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
    10. Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol. 2005 Sep. 153(3):521-5.
    11. Brice SL. Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Jan. 83(1):14-20.
    12. Femiano F, Buonaiuto C, Gombos F, Lanza A, Cirillo N. Pilot study on recurrent aphthous stomatitis (RAS): a randomized placebo-controlled trial for the comparative therapeutic effects of systemic prednisone and systemic montelukast in subjects unresponsive to topical therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Mar. 109(3):402-7.
    13. de Abreu MA, Hirata CH, Pimentel DR, Weckx LL. Treatment of recurrent aphthous stomatitis with clofazimine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Nov. 108(5):714-21.
    14. Arikan OK, Birol A, Tuncez F, Erkek E, Koc C. A prospective randomized controlled trial to determine if cryotherapy can reduce the pain of patients with minor form of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Jan. 101(1):e1-5.
    15. Eversole LR, Shopper TP, Chambers DW. Effects of suspected foodstuff challenging agents in the etiology of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1982 Jul. 54(1):33-8.
    16. Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol. 1984 May. 57(5):504-7.
    17. Wright A, Ryan FP, Willingham SE, et al. Food allergy or intolerance in severe recurrent aphthous ulceration of the mouth. Br Med J (Clin Res Ed). 1986 May 10. 292(6530):1237-8.
    18. Axell T, Henricsson V. Association between recurrent aphthous ulcers and tobacco habits. Scand J Dent Res. 1985 Jun. 93(3):239-42.
    19. Bittoun R. Recurrent aphthous ulcers and nicotine. Med J Aust. 1991 Apr 1. 154(7):471-2.

    • [Recurrent aphthous stomatitis: treatment with colchicine. An open trial of 54 cases] - V Fontes, L Machet, B Huttenberger - de dermatologie et de , 2002 - ukpmc.ac.uk
    • Aphthous ulceration - C Scully - New England Journal of Medicine, 2006 - Mass Medical Soc
    • Detection of Helicobacter pylori DNA in recurrent aphthous stomatitis tissue by PCR - MP Riggio, A Lennon, D Wray - Journal of oral pathology & , 2002 - Wiley Online Library
    • A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers - RO Greer, JE Lindenmuth, T Juarez - Journal of oral and , 1993 - Elsevier
    • Burning mouth syndrome and peripheral neuropathy in patients with type 1 diabetes mellitus - PA Moore, J Guggenheimer, T Orchard - Journal of diabetes and its , 2007 - Elsevier
    • Association between Helicobacter pylori and recurrent aphthous stomatitis in children and adolescents - AMG Fritscher, K Cherubini, J Chies - Journal of oral , 2004 - Wiley Online Library
    • Clinical, historic, and therapeutic features of aphthous stomatitis: Literature review and open clinical trial employing steroids - SD Vincent, GE Lilly - Oral surgery, oral medicine, oral pathology, 1992 - Elsevier

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