Aphthous stomatitis (Canker sores, recurrent aphthous stomatitis, RAS)

DESCRIPTION:   This is one of the most common oral diseases. The exact incidence is unknown, but estimates range from 20% to 60% of the population. Lesions appear as painful ulcers ranging in size from less than 1 mm to 2 centimeters. They may be single or multiple. Small lesions (less than 0.5 cm) have been referred to as minor aphthae (Fig. 1) and large lesions (more than 0.5 cm) have been called major aphthae (Fig. 2).

An uncommon presentation of this disease appears as multiple, pinpoint areas of ulceration that seldom exceed 1 mm (Fig. 3). This has been referred to as the herpetiform pattern, an unfortunate terms since herpes virus is not the cause.

Each lesion begins as a red macule, less often a papule but not as a blister. It soon ulcerates and the ulcer becomes covered by a pyogenic membrane producing the characteristic yellow-white center with surrounding erythematous flare. The shape is usually round to oval but may be elongated in natural folds such as the vestibule.

Aphthous stomatitis occurs on freely movable mucosa that does not overlie bone. The lips, cheeks, soft palate, floor of mouth, ventral and lateral tongue are often involved but attached gingival, hard palate and dorsal tongue are seldom affected.

Aphthous lesions affect all age groups from young to old but young adults and females are more affected. Elapsed time between recurrences is extremely variable; some unfortunate patients have almost continuous disease whereas others go from months to years between episodes.

ETIOLOGY:  The cause is unknown. The concept that canker sores are caused by a microbiologic agent has been superceded by theories revolving around an immunopathogenesis. The deposition of antibodies and complement within epithelium and basement membrane during the early stages of the disease suggests a humoral immune response, and the  influx  of  lymphocytes  rather  than  neutrophils  in  early  lesions  points  to  a  cellular immune reaction as well. It is yet to be learned if the immune response is directed against self (autoimmunity) or against an extrinsic antigen such as bacteria or viruses. To further cloud the issue, a variety of other factors have been implicated.

Withdrawal of certain foods such as cheese, tomato products and gluten, as well as sodium lauryl sulfate-containing tooth pastes, has been claimed to help some patients whereas in others, correction of iron, B12 and folate deficiencies have brought about a cure. Improvement of aphthous lesions during the last stages of pregnancy with exacerbation after delivery suggests that gonadal hormones may lay a role. The occurrence of canker sores during menstruation also suggests a hormonal basis. To add a final element of mystery, aphthous stomatitis has been reported to worsen when cigarette smoking is discontinued. There are too many theories for them all to be correct. Aphthous stomatitis may not be a single disease with a single cause but instead a variety of diseases all manifested by painful mouth sores.

TREATMENT:   To reduce pain, patients with few lesions may be treated with topical medications such as Orabase  ® with Benzocaine, Zilactin ®, or Soothe-N-Seal  ®. Anti-inflammatory agents such as topical steroids or Aphthasol  ® have also been shown to be effective. For severe or widespread disease, systemic prednisone such as a Medrol 4 mg Dosepak  ® is helpful. Long-term systemic steroid therapy may be associated with numerous adverse effects, including osteoporosis, asceptic necrosis, cataracts, depression, fluid retention and exacerbation of diabetes.

PROGNOSIS:  Cure is seldom achieved but palliation and long-term remission may be achieved by above mentioned treatment. Without treatment, healing time varies from 4 days for a small lesion to a month or more for major aphthae. Major aphthae may also cause scarring.

DIFFERENTIAL DIAGNOSIS:  Aphthous stomatitis must be differentiated from herpetic stomatitis, the disease with which it is most often confused. Recurrent intraoral herpes occurs almost exclusively on mucosa overlying bone. The hard palate is the most common site. Lesions indistinguishable from aphthous stomatitis have been reported in Behcet's syndrome, Reiter's syndrome, Crohn's disease and celiac disease.

Herpes simplex virus infections

DESCRIPTION:   

Oral infection with herpes simplex virus occurs in three clinical forms. The most common type consists of recurrent small blisters on the lips commonly referred to as fever blisters or secondary herpes labialis. The second type is a generalized oral infection called primary herpetic stomatitis. The third and least common form of oral herpes infection consist of small ulcers usually localized on palatal mucosa.

Herpes labialis is illustration in Figs. 1 and 2. This lesion is well known and unlikely to be  a  diagnostic  problem.  It  tends  to  be  a  recurrent  disease  in  teenagers  and  adults. Elapsed time between recurrences varies from person to person. Recurrences are thought to be triggered by exposure to sunlight, febrile diseases, physical and psychogenic trauma, and other irritants.

Generalized involvement of the oral mucous membrane is called primary herpetic stomatitis and represents the initial exposure to the virus. This is a one time infection, but the patient remains susceptible to recurrent or secondary oral herpes infections (Figs. 3 and 4).

  It  is  more  commonly  seen  in  children,  but  teenagers  and  adults  are  also  affected.

Patients initially have gingivitis with swollen and red gingiva, then small blisters may appear on other mucosal surfaces. The blisters break quickly and are seldom seen by the dentist or physician. After they break, the lesions appear as small ulcers that resemble small aphthous lesions. The primary, generalized infection is accompanied by fever, cervical lymphadenitis, and inability to eat or drink without considerable pain. Patients who suffer recurrent intraoral herpes are few. Recurrent intraoral herpes infections  tend  to  occur  as  vesicles  followed  by  small  ulcers,  mainly  on  the  hard  palate mucosa (Fig. 5) and often follow trauma to the area, such as palatal injections or periodontal therapy.

ETIOLOGY:  

Herpesvirus hominis (herpes simplex virus). Most oral lesions are caused by Type I virus but approximately 10% are thought to be caused by Type II.

TREATMENT:   

Antiviral drugs such as Acyclovir, Famciclovir, Penciclovir, Valacyclovir and over-the-counter Abreva have all shown that they can decrease the time of disease as well as help with pain management. To be beneficial, they must be started at the first sign of disease. Most studies indicate that the drugs decrease the duration of disease by about one day. Acyclovir, Penciclovir and Abreva are available in a topical ointment.

PROGNOSIS:     

Primary  infection  usually  resolves  in  10-14  days.  Once  the  virus  has entered the body, it travels through nerve trunks to the nearest ganglion where it may lie dormant  for  the  remainder  of  the  patient's  life.  Future  recurrences  are  thought  to  be brought about by the "reawakening" of the virus which retraces its steps to cause new lesions in the same general area as the original point of entry. Thus, each recurrence is not a new and different infection from the outside but a recrudescence of the original infection. The ability of the virus to remain latent in deep ganglia makes total eradication almost impossible and will likely frustrate attempts at prevention for the foreseeable future.

Patients with widespread herpetic stomatitis should drink liquids to prevent dehydration. A broad-spectrum antibiotic is commonly given to control secondary bacterial infection, but does not shorten the viral infection. Antiviral drugs may shorten the duration of the disease if they are started early.

Clinicians should be aware that the herpesvirus may cause disseminated infection including encephalitis in which case the prognosis is extremely grave.

DIFFERENTIAL DIAGNOSIS:   

Primary herpetic stomatitis may resemble oral lesions of erythema multiforme, but herpes can be diagnosed by exfoliative cytology.A characteristic multinucleated cell appears in the smear of herpes infections. Culture of the virus is possible if a viral laboratory is available. Lesions of herpangina and hand, foot and mouth disease, both caused by Coxsackievirus, may clinically resemble oral herpes virus infections. Recurrent intraoral herpes may be confused with herpes zoster. Aphthous can be differentiated since it usually does not occur over bone, does not form vesicles and is not accompanied by fever or gingivitis.

Varix (plural: varices)

DESCRIPTION:  Varices appear as red, blue, or deep purple broad-based elevations in  oral mucosa. The size is usually less than 5 mm. The buccal mucosa is a common place to find them, however, they are also found in lip mucosa and ventral and lateral mucosa of the tongue and floor of the mouth. On ventral tongue they are apt to be multiple and the term "caviar tongue" has been commonly used to describe them. They are seen more commonly in the elderly.

ETIOLOGY:  A varix is a distended vein that elevates the overlying mucosa.  The reason  for  venous  distention  is unclear  but  may  be  related  to  weakening  of  the  vessel wall secondary to aging.

TREATMENT:  None usually required. They often thrombose but this is of little clinical consequence.

PROGNOSIS:  Good

DIFFERENTIAL DIAGNOSIS:  Mucocele, hemangioma and angina bullosa hemorragica. 

Snuff lesion (smokeless tobacco lesion)

DESCRIPTION:  The lesion develops on the mucosa where smokeless tobacco is held.  The usual appearance is white, wrinkled or corrugated mucosa. Gingival recession is a  common manifestation with cervical erosion of teeth a less frequent finding. Symptoms are uncommon.

ETIOLOGY:    Prolonged  use  of  smokeless  tobacco  produces such as chewing tobacco or snuff.

TREATMENT:  Biopsy should be done to rule out dysplasia, otherwise no treatment is necessary.

PROGNOSIS:  Verrucous and squamous carcinomas arise in smokeless tobacco lesions more than chance alone can explain. One article noted almost a 50-fold increased risk of cancers of the gingival  and  buccal  mucosa in females who were chronic users. The duration necessary   to   induce   dysplastic   or   malignant   change   is unknown but appears to be at least 20 years.

DIFFERENTIAL  DIAGNOSIS:   The clinical appearance of the  lesion  plus  a  history  of  using  smokeless  tobacco establishes the diagnosis.

Acquired immune deficiency syndrome (AIDS) and its oral manifestations

Description:  Acquired immune deficiency syndrome is characterized by relentless destruction of CD4 T lymphocytes, key cells of the immune system. The eventual collapse of both the cellular and humoral arms of immunity leaves the host vulnerable to  a wide variety of pathogenic organisms including bacteria, viruses, fungi and protozoa.  It is important for health care workers to recognize that it is difficult to transmit the AIDS virus in the health care setting, from patient to worker or the reverse. However, opportunistic infectious diseases that AIDS patients are apt to have including tuberculosis, herpes-virus infections, hepatitis B and hepatitis C are readily transmissible.

Etiology:  The causes of AIDS is an RNA  retrovirus of the lentivirus group. It is designated the human immunodeficiency virus (HIV) and there are several variants:  HIV- 1 is the most common cases of AIDS. The virus attaches to the surface of cells that bear the  CD4  receptor  including  helper  T  lymphocytes,  B  lymphocytes  and  macrophages.

Although they lack a CD4 receptor, microglia, skin fibroblasts, and bowel epithelium become  infected.  The  virus  destroys  the  infected  cells.  With  gradual  depletion  of  the cells of immunity, especially T-helper lymphocytes and macrophages, the host becomes increasingly vulnerable to pathogenic organisms.

Oral Manifestations:

Candidiasis  -  Colonization  and  infection  of  the  oral  mucosa  by  Candida  species  is among the earliest and most common findings in HIV-infected patients. In one study, 88% had oral candidiasis. Lesions range from white to red or red/white combinations.

Fig. 1 illustrates the typical appearance of candidiasis. The lesions may be asymptomatic or there may be mild discomfort. For stubborn infection, fluconazole is recommended.  

Kaposi's  sarcoma  -  AIDS  patients  are  vulnerable  to  a  variety  of  oral  malignancies including Kaposi's sarcoma, malignant lymphoma and squamous carcinoma. Kaposi's sarcoma is the most common. In one study, 20% of AIDS patients had Kaposi's sarcoma and of these, the tumor was in the oral cavity in 1 of every 5 patients; the palate is the most common site. In the early stage, the tumor appears as a red to purple bruise (Fig. 2). The tumor grows and eventually appears as a hemorrhagic mass (Fig. 3). The cell of origin  is  endothelium;  thus  Kaposi's  sarcoma  is  a  variety  of  angiosarcoma.  They  are locally invasive, cause pain and bleeding and interfere with normal function. Low-dose radiation  therapy  and  intralesional  or  systemic  chemotherapy  are  the  treatments  of choice. Herpes virus type VIII is thought to play a role in the pathogenesis of this tumor.

Hairy leukoplakia  -  This  variety  of  leukoplakia  was  first  recognized  in  HIV-infected patients but has been encountered in other immune deficiency states such as organ transplant patients who are intentionally immune suppressed. The lateral tongue is the most common location (Fig. 4). Lesions are of rough texture, adherent and asymptomatic. The diagnosis of hairy leukoplakia can be suspected on routine biopsy specimens, but confirmation requires demonstration of the presence of the causative virus, the Epstein-Barr herpesvirus. This is ordinarily achieved by DNA in situ hybridization. A word of caution: hairy leukoplakia may be confused with candidiasis. A patient who presents with a white lesion should be treated with antifungal therapy first. If it fails to heal, it most likely is hairy leukoplakia.

Gingival and periodontal lesions  - HIV-infected patients are vulnerable to necrotizing gingivitis and periodontitis (Fig. 5). The organisms recovered from these lesions are the same as those in non-HIV-positive patients. Lesions are treated by dental prophylaxis, debridement, and metronidazole. Good oral hygiene and daily rinses with chlorhexidine are beneficial.

Others - HIV patients also develop major aphthous-like lesions that respond to tetracycline and topical steroid therapy.

Thalidomide has been used successfully in their management. The human papillomavirus has also been found in both condylomas and focal epithelial hyperplasia. Cytomegalovirus infections and several fungal infections such as histoplasmosis  and  coccidiodomycosis  are  also  common.  Lastly,  xerostomia  secondary  to  salivary  gland  destructions  has  been reported.