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Canker sores are shallow, painful sores in your mouth that are usually red and may sometimes have a
white coating over them. Canker sores often appear on the inside of your lips and cheeks, the base of
your gums or under your tongue. Canker sores are different from fever blisters, which are usually on the
outside of your lips or the corners of your mouth.

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Doctors do not know what causes canker sores, but they may be triggered by physical or psychological
stress, poor nutrition, food allergies, viral or bacterial infection, chemical irritations, menstrual periods and
trauma. Also orthodontic appliances, for example braces, cause canker sores.


No one knows what causes canker sores. The vast majority of people who develop canker sores do not
have another problem as the cause.

` Both hereditary and environmental causes of the disease have been suggested, but the exact
cause is not clear.
` A number of factors have been suggested to precipitate outbreaks in susceptible individuals;
however, none has been proven to be the cause in all people.
„ oral trauma
„ hormonal changes related to the menstrual cycle
„ anxiety or stress
„ smoking cessation
„ heredity
„ drugs (including anti-inflammatory drugs, such as ibuprofen [Motrin], and beta-blockers,
such as atenolol [Tenormin])
„ food allergies or sensitivities (chocolate, tomatoes, nuts, and acidic foods such as
pineapple, and preservatives such as benzoic acid and cinnamaldehyde)
„ toothpastes containing sodium lauryl sulfate
„ deficiencies of iron, folic acid, or vitamin B12 (although supplementation with iron or
vitamins has not been shown to decrease the likelihood of ulcer resolution)
` Some studies have suggested an association with u
 

, the same bacteria that
cause peptic ulcers. Recent studies have suggested that treatment of the u
 


infection may improve symptoms or completely stop recurrent disease in some patients.

` Recurrent canker sores have been associated with inflammatory bowel diseases, such as Crohn
disease and ulcerative colitis. In these cases, the development of canker sores may signal a
flare-up of the bowel disease.
` Celiac, or abdominal, sprue, a disease of the intestines caused by sensitivity to gluten, causes
malabsorption and is associated with development of canker sores. Gluten refers to a group of
proteins found in wheat, barley, and rye.
` Behèet's disease is a condition characterized by canker sores, genital sores that resemble
canker sores, and inflammation of the eye.
` Infection with the AIDS virus also has been associated with canker sores.
` It is a common misconception that canker sores are a form of herpes infection. This is not the
case.



  



The etiology of recurrent aphthous stomatitis (RAS) is not entirely clear, and aphthae are therefore
termed idiopathic. RAS may be the manifestation of a group of disorders of quite different etiology, rather
than a single entity.
Despite many studies trying to identify a causal microorganism, RAS does not appear to be infectious,
contagious, or sexually transmitted. Immune mechanisms appear at play in persons with a genetic
predisposition to oral ulceration.

A genetic basis exists for some RAS. This is shown by a positive family history in about one third of
patients with RAS, an increased frequency of HLA types A2, A11, B12, and DR2, and susceptibility to
RAS which segregates in families in association with HLA haplotypes. RAS probably involves cell-
mediated mechanisms, but the precise immunopathogenesis remains unclear. Phagocytic and cytotoxic T
cells probably aid in destruction of oral epithelium that is directed and sustained by local cytokine release.

Patients with active RAS have an increased proportion of gamma-delta T cells compared with control
subjects and patients with inactive RAS. Gamma-delta T cells may be involved in antibody-dependent
cell-mediated cytotoxicity (ADCC). Compared with control subjects, individuals with RAS have raised
serum levels of cytokines such as interleukin (IL)±6 and IL-2R, soluble intercellular adhesion modules
(ICAM), vascular cell adhesion modules (VCAM), and E-selectin; however, some of these do not correlate
with disease activity.

Cross-reactivity between a streptococcal 60- to 65-kd heat shock protein (hsp) and the oral mucosa has
been demonstrated, and significantly elevated levels of serum antibodies to hsp are found in patients with
RAS. Lymphocytes of patients with RAS have reactivity to a peptide of ½   

Some cross-reactivity exists between the 65-kd hsp and the 60-kd human mitochondrial hsp. Monoclonal
antibodies to part of the 65-kd hsp of ½  
 react with 
  RAS thus may be
a T cell±mediated response to antigens of  , which cross-react with the mitochondrial hsp and
induce oral mucosal damage. RAS patients have an anomalous activity of the toll-like receptor TLR2
pathway that probably influences the stimulation of an abnormal Th1 immune response.

Predisposing factors found may include any of the following:

` Hematinic deficiency: Up to 20% of patients are deficient of iron, folic acid (folate), or vitamin B.
` Malabsorption in gastrointestinal disorders: About 3% of patients experience these disorders,
particularly celiac disease (gluten-sensitive enteropathy) but, occasionally, Crohn disease,
pernicious anemia, and dermatitis herpetiformis. HLA DRW10 and DQW1 may predispose
patients with celiac disease to RAS.
` Cessation of smoking: This may precipitate or exacerbate RAS in some cases.
` Stress: This underlies RAS in some cases; ulcers appear to exacerbate during school or
university examination times.
` Trauma: Biting of the mucosa and wearing of dental appliances may lead to some ulcers; RAS is
uncommon on keratinized mucosae.
` Endocrine factors in some women: RAS is clearly related to the progestogen level fall in the luteal
phase of the menstrual cycle, and ulcers may then temporarily regress in pregnancy.
` Allergies to food: Food allergies occasionally underlie RAS; the prevalence of atopy is high.
Patients with aphthae may occasionally have a reaction to cow's milk, and may have been
weaned at an early age.
` Sodium lauryl sulphate (SLS): This is a detergent in some oral healthcare products that may
aggravate or produce oral ulceration.
` Immune deficiencies: Ulcers similar to RAS may be seen in patients with HIV, neutropenias and
some other immune defects.
` Drugs, especially NSAIDs, alendronate, and nicorandil: These may produce lesions clinically
similar to RAS.


 





RAS affects 5-66% of the population in US. Approximately 1% of children from higher socioeconomic
groups in developed countries have RAS; however, 40% of selected groups of children can have a history
of RAS, with ulceration beginning before age 5 years and with the frequency of affected patients
increasing with age.






Most patients with RAS are otherwise well.




RAS have been reported in all races



A slight female predominance exists.



RAS typically starts in childhood or adolescence.

 


The 3 main clinical types of recurrent aphthous stomatitis (RAS) are as follows:

(1) Minor aphthous ulcers (MiAUs, 80% of all RAS)

(2) Major aphthous ulcers (MjAUs)

(3) Herpetiform ulcers.

However, any significance of these distinctions is unclear (ie, they could just be 3 distinct disorders).
Diagnosis is based on history and clinical features.

Characteristics of MiAUs (ie, Mikulicz ulcers) include the following:

` They occur mainly in persons 10-40 years of age.

` They often cause minimal symptoms.
` They are small round or ovoid ulcers 2-4 mm in diameter. (MiAUs are round or ovoid in most
situations but are often more linear when in the buccal sulcus, a common site.)
` They have an ulcer floor that is initially yellowish but assumes a gray hue as healing and
epithelialization proceeds.
` They are surrounded by an erythematous halo and some edema.
` They are found mainly on the nonkeratinized mobile mucosa of the lips, cheeks, floor of the
mouth, sulci, or ventrum of the tongue; they are uncommonly seen on the keratinized mucosa of
the palate or dorsum of the tongue.
` They occur in groups of only a few ulcers (ie, 1-6) at a time.
 ` They heal in 7-10 days.
` They recur at intervals of 1-4 months.
` They leave little or no evidence of scarring.

Characteristics of MjAUs (ie, Sutton ulcers, periadenitis mucosa necrotica recurrens [PMNR]) include the
following:

` They are larger, of longer duration, of more frequent recurrence, and often more painful than
MjAUs.
` They are round or ovoid like MjAUs but are larger and associated with surrounding edema.
` They reach a large size, usually about 1 cm in diameter or even larger.
` They are found on any area of the oral mucosa, including the keratinized dorsum of the tongue or
palate.
` They occur in groups of only a few ulcers (ie, 1-6) at one time.
` They heal slowly over 10-40 days.
` They recur extremely frequently.
` They may heal with scarring.
` They occasionally are found with a raised erythrocyte sedimentation rate or plasma viscosity.

Characteristics of herpetiform ulceration (HU) include the following:

` They are found in a slightly older age group than the other RAS.
` They are mainly found in females.
` They begins with vesiculation that passes rapidly into multiple, minute, pinhead-sized, discrete
ulcers.
` They involve any oral site, including the keratinized mucosa, increase in size, and coalesce to
leave large round ragged ulcers.
` They heal in 10 days or longer.
` They are often extremely painful.
` They recur so frequently that ulceration may be virtually continuous.

Most patients appear to be otherwise well, but a minority have etiologic factors that can be identified by
the history. These factors may include the following:

` Dentifrices containing sodium lauryl sulfate

` Trauma
` Stress
` Cessation of smoking
` Menstrual cycle association
` Food allergy

Aphthous-like ulcers may appear in the following diseases and states:

` Hematinic deficiency (eg, iron, folate, vitamin B-12)

` Celiac disease
` Crohn disease
` Behçet syndrome, which may include genital, cutaneous, ocular, or other lesions (The mouth
ulcers in Behçet syndrome are often major aphthae, with frequent episodes and long duration to
healing.)
` Immunodeficiencies such as human immunodeficiency virus (HIV) infection, and neutropenia
(Ulcers appearing on a regular 3-week cycle may indicate cyclic neutropenia.)
 ` Auto-inflammatory syndromes, such as periodic fever, aphthous stomatitis, pharyngitis, and
cervical adenitis syndrome (PFAPA) in children
` Malignancy (Ulcers appearing for the first time in an older individual may reflect underlying
systemic disease [eg, colonic carcinoma with chronic hemorrhage].)
` Drug use (eg, nicorandil, NSAIDs, others)
` Sweet syndrome, a rare immunologically mediated condition that belongs to the group of
neutrophilic dermatoses and must be differentiated, particularly from Behçet disease
„ Sweet syndrome is characterized by red-brown plaques and nodules that are frequently
painful and occur primarily on the head, neck, and upper extremities.
„ Patients often also have neutrophilia and fever and may have oral ulceration.

! 


 
 
  

` Aspirin
` Barbiturates (used for insomnia)
` Chemotherapy drugs for cancer
` Gold (used for rheumatoid arthritis)
` Penicillin
` Phenytoin (used for seizures)
` Streptomycin
` Sulfonamides

  


RAS ulcers are recurrent small, round, or ovoid ulcers with circumscribed margins, erythematous haloes,
and yellow or gray floors. No specific investigations exist for RAS.

Some RAS cases involve a familial and genetic basis; approximately 40% of patients with RAS have a
familial history, but inheritance may be polygenic with penetrance dependent on other factors.

` Most relevant studies have found hematinic (eg, iron, folic acid, vitamin B-12) deficiencies in as
many as 20% of patients with recurrent ulcers. In addition, deficiencies of vitamins B-1, B-2, and
B-6 have been noted in some patient cohorts.
` The previously proposed association between recurrent ulcers and celiac disease (gluten-
sensitive enteropathy [GSE]) is tenuous, despite some evidence that the haplotype of HLA-DRW
10 and DQW1 may predispose patients with GSE to RAS.
` Hypersensitivity reactions to exogenous antigens other than gluten do not have a significant
etiologic role in RAS, and associations with atopy are inconsistent.
` Local physical trauma may initiate ulcers in susceptible people, and RAS is uncommon where
mucosal keratinization is present or in patients who smoke tobacco.
` A consistent association between aphthouslike ulceration and psychological illness, zinc
deficiency, or sex hormone levels is unlikely.
` Various microorganisms have been examined for a causal association. Latterly, u
 


 has been detected in lesional tissue of ill-defined oral ulcers, but the frequency of serum
immunoglobin G (IgG) antibodies to u

 is not increased in RAS. Little evidence suggests an
etiologic association between viruses and RAS. Human herpesviruses (HHV)±6 and HHV-7 DNA
have not been demonstrated in RAS, but HHV-8 DNA is present in HIV-related oral ulcers.

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` Systemic disorders should particularly be suspected in the presence of features that may suggest
a systemic background.
 ` Diagnosis of recurrent aphthous stomatitis (RAS) is based on history and clinical features. No
specific tests are available; however, to exclude systemic disorders discussed above, the
following tests may be helpful:
„ Complete blood cell count
„ Hemoglobin test
„ White blood cell count with differential
„ Red blood cell indices
„ Iron studies (usually an assay of serum ferritin levels)
„ Red blood cell folate assay
„ Serum vitamin B-12 measurements
„ Serum antiendomysium antibody and transglutaminase assay (positive in celiac disease)
` Rarely, biopsy may be indicated in cases in which a different diagnosis is suspected.

 

 

The histology is nonspecific. The ulcer is depressed well below the surface, and the inflammation extends
deeply. The surface of the ulcer is covered by a fibrinous exudate infiltrated by polymorphs. Beneath is a
layer of granulation tissue with dilated capillaries and edema. Deeper still is a repair reaction, with
fibroblasts in the surrounding connective tissue laying down fibrous tissue.





Identify and correct predisposing factors for recurrent aphthous stomatitis (RAS). Ensure that patients
brush atraumatically (eg, with a small-headed, soft toothbrush) and avoid eating particularly hard or sharp
foods (eg, toast, potato crisps) and avoid other trauma to the oral mucosa.

SLS should be avoided if implicated as a predisposing factor. Any iron or vitamin deficiency should be
corrected once the cause of that deficiency has been established. If an obvious relationship to certain
foods is established, these should be excluded from the diet. Patch testing may be indicated to reveal
allergies. The occasional patient who relates ulcers to her menstrual cycle or to use of an oral
contraceptive may benefit from suppression of ovulation with a progestogen or a change in the oral
contraceptive. Causal drugs should be excluded.

In most cases, the natural history of RAS is one of eventual remission. However, for some patients,
remission occurs spontaneously several years later; thus, treatment is indicated in these patients if
discomfort is significant. Relief of pain and reduction of ulcer duration are the main goals of therapy.
Objective evidence shows the most efficacy from corticosteroids and antimicrobials used topically.

` Vitamin B12 used orally may have some effect

` Topical corticosteroids (TCs) remain the mainstays of treatment. A spectrum of different TCs can
be used. At best, TCs reduce painful symptoms but not the rate of ulcer recurrence. The
commonly used preparations are as follows:
„ Hydrocortisone hemisuccinate pellets (Corlan), 2.5 mg used 4 times daily
„ Triamcinolone acetonide in carboxymethyl cellulose paste (Adcortyl in orabase
[withdrawn in some countries], Kenalog), administered 4 times daily
„ Betamethasone sodium phosphate as a 0.5-mg tablet dissolved in 15 mL of water to
make a mouth rinse, used 4 times daily for 4 minutes each time
` Hydrocortisone and triamcinolone preparations are popular because neither causes significant
adrenal suppression; however, ulcers still recur.
` Betamethasone, fluocinonide, fluocinolone, fluticasone, and clobetasol are more potent and
effective than hydrocortisone and triamcinolone, but they carry the possibility of some
adrenocortical suppression and a predisposition to candidiasis.
 ` Topical tetracyclines may reduce the severity of ulceration, but they do not alter the recurrence
rate. A doxycycline capsule of 100 mg in 10 mL of water administered as a mouth rinse for 3
minutes or tetracycline 500 mg plus nicotinamide 500 mg administered 4 times daily may provide
relief and reduce ulcer duration. Avoid tetracyclines in children younger than 12 years who might
ingest them and develop tooth staining.
` Chlorhexidine gluconate mouth rinses reduce the severity and pain of ulceration but not the
frequency.
` Anti-inflammatory agents can help; a spectrum of topical agents such as benzydamine and
amlexanox may help. Benzydamine hydrochloride mouthwash, though no more beneficial than a
placebo, can produce transient pain relief.
` If RAS fails to respond to local measures, systemic immunomodulators may be required. A wide
spectrum of agents has been suggested as beneficial, but few studies have been performed to
assess their efficacy (or their adverse effects are significant). Thalidomide 50-100 mg daily is
effective against severe RAS, although ulcers tend to recur within 3 weeks. Teratogenicity,
neuropathy, and other adverse effects dissuade most physicians from its use.
` Few, if any, of the other medications used for RAS have undergone serious scientific evaluation.
These include transfer factor, gamma-globulin therapy, sodium cromoglycate lozenges, dapsone,
colchicine, pentoxifylline, levamisole, colchicine, azathioprine, prednisolone, azelastine, alpha 2-
interferon, ciclosporin, deglycerinated liquorice, 5-aminosalicylic acid (5-ASA), prostaglandin E2
(PGE2), sucralfate, diclofenac, and aspirin.


  

 

` Gastroenterologist
` Immunologist/allergologist
` Hematologist
` Rheumatologist






` TCs remain the mainstay of treatment for recurrent aphthous stomatitis (RAS). TCs reduce the
number of ulcer days compared with controls, but they have no consistent effect on the frequency
of ulceration. TCs may reduce the ulcer duration and pain. Amlexanox oral adhesive pellicles or
oral adhesive tablets appear to reduce ulcer pain and duration.
` Chlorhexidine gluconate mouth rinses reduce the severity and pain of ulceration but do not affect
the frequency.
` The range of systemic medications available is of variable or unproven efficacy or may have
serious adverse effects; such agents include systemic corticosteroids, colchicine, clofazimine,
and thalidomide (and many others).




 




A spectrum of different TCs can be used. All can reduce symptoms, and neither hydrocortisone
nor triamcinolone preparations cause adrenal suppression. Ulcers still recur.

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decrease inflammation and cause vasoconstriction.

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Anyone can get canker sores, however, women, teens and people in their 20s suffer from canker sores
most frequently. Canker sores are not contagious.

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Aphthasol is the only FDA - approved medicament that helps you manage your canker sores. Early
treatment is the key to a fast healing.

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Unfortunately, doctors don't know of anything that prevents canker sores from forming. Using a
toothpaste that does not contain SLS (sodium lauryl sulfate) or other irritating ingredients, avoiding hard,
crunchy or spicy foods and chewing gum may help reduce mouth irritation. Brushing your teeth after
meals, using a soft toothbrush and flossing every day will also keep your mouth free of food that might
cause a canker sore.

Canker Sores vs. Cold Sores

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 (aphthous ulcers)
Definition Cold sores (aka fever blisters), are clusters of Canker sores are small shallow ulcers that
small blisters on the lip and outer edge of the appear in the mouth and often make it
mouth. The skin around the blisters is often uncomfortable to eat and talk. The exact
red and inflamed. The blisters can break cause of most canker sores is unknown.
open, weep a clear fluid, and then scab over Stress or tissue injury is thought to be one.
after a few days. Complete healing may take Certain foods - including citrus or acidic fruits
7 to 10 days. and vegetables (such as lemons, oranges,
pineapples, apples, figs, tomatoes,
strawberries) - can trigger a canker sore or
make the problem worse. Use of nonsteroidal
anti-inflammatory drugs, like Motrin, is another
common cause. Sometimes a sharp tooth
surface or dental appliance, such as braces or
ill-fitting dentures, can also trigger canker
sores. Some cases of 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; and
gastrointestinal tract disease, such as Celiac
disease and Crohn's disease.
Symptoms You can be infected with herpes simplex virus A painful sore or sores inside your mouth - on
(HSV-1) and have no symptoms. For some the tongue, soft palate (the back portion of the
people, cold sores can be painful. Initial roof of your mouth), or inside your cheeks. A
symptoms may include mouth soreness, tingling or burning sensation prior to the
fever, sore throat, or swollen lymph glands. appearance of the sores. Sores in your mouth
Small children sometimes drool before a cold that are round, white, or gray in color, with a
sore appears. After the cold sores develop, red edge or border. Severe attacks may
blisters usually break open, weep clear fluid, include fever, physical sluggishness and
and then crust over and disappear after swollen lymph nodes.
several days to a week.
Diagnosis Your health professional can diagnose cold Your health care professional can diagnose
sores by asking you questions to determine canker sores by asking you questions and by
whether you have been exposed to the HSV examining you. No further testing is usually
and by examining you. No further testing is needed.
usually needed.
Treatment Cold sores will usually go away on their own If sores are large, painful, or persistent, your
within a few days. However, if they are severe dentist may prescribe an antimicrobial mouth
or cause you embarrassment or discomfort, rinse, a corticosteroid ointment, or a
cold sores can be treated. Treatment may prescription or nonprescription solution to
include topical creams or ointments or reduce the pain and irritation.
sometimes antiviral medicines (such as
acyclovir or famciclovir). Treatment may
lessen the duration of the cold sores by 1 to 2
days, but can help soothe pain or other
uncomfortable symptoms. There is no know
cure for the herpes simplex virus (HSV-1) that
causes cold sores. If sores develop regularly,
treatment can reduce the number and severity
of outbreaks.
How they The herpes simplex virus (HSV) usually Canker Sores are not contagious.
are Spread enters your body through a break in the skin
around or inside your mouth. It is spread
through coughing, sneezing, direct contact
with a cold sore, or touching contaminated
fluid-such as from kissing an infected person
and touching their saliva. The virus can also
be spread from one person to an area of
someone else's body by touching an active
cold sore or sharing things that a person who
has a cold sore has used. A parent who has a
cold sore often spreads the infection to his or
her child.
Where can I get more information about Canker-Sores?
Ask your personal Healthcare Professional to get more information about canker sores!

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Aphthasol is clinically proven to promote 72% faster healing and significantly reduce the discomfort while
having cankers sores. The earlier you use it, the faster it heals!

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Clinical studies show that pain caused by a canker sore can be momentously reduced by applying
Aphthasol. Experience the efficacy of Aphthasol and get relief now!