Actinic cheilitis (also known as "Actinic cheilosis"

[1]
) is a form of cheilitis which is the counterpart of actinic
keratosisof the skin and can develop into squamous cell carcinoma. In actinic cheilitis, there is thickening whitish
discoloration of the lip at the border of the lip and skin. There is also a loss of the usually sharp border between the
red of the lip and the normal skin, known as the vermillion border. The lip may become scaly and indurated as
actinic cheilitis progresses. The lesion is usually painless, persistent, more common in older males, and more
common in individuals with a light complexion with a history of chronic sun exposure.
Contents
[hide]
1 Causes
2 Treatment options
o 2.1 Medication
o 2.2 Procedures
3 References
Causes[edit]
Actinic cheilitis is caused by chronic and excessive exposure to ultraviolet radiation in sunlight. Additional factors may
also play a role, including tobacco use, lip irritation, poor oral hygiene, and ill-fitting dentures.
[2]

Treatment options[edit]
This condition is considered premalignant because it may lead to squamous cell carcinoma in about 10% of all cases.
It is not possible to predict which cases will progress into SCC, so the current consensus is that all lesions should be
treated.
[3]

Treatment options include 5-fluorouracil, imiquimod, scalpel vermillionectomy, chemical peel, electrosurgery,
and carbon dioxide laser vaporization. These curative treatments attempt to destroy or remove the
damaged epithelium. All methods are associated with some degree of pain, edema, and a relatively low rate of
recurrence.
Medication[edit]
Topical 5-fluorouracil (5-FU, Efudex, Carac) has been shown to be an effective therapy for diffuse, but minor actinic
cheilitis. 5-fluorouracil works by blocking DNAsynthesis. Cells that are rapidly growing need more DNA, so they
accumulate more 5-fluorouracil, resulting in their death. Normal skin is much less affected. The treatment usually
takes 2-4 weeks depending on the response. The typical response includes an inflammatory phase, followed by
redness, burning, oozing, and finally erosion. Treatment is stopped when ulceration and crusting appear. There is
minimal scarring. Complete clearance has been reported in about 50% of patients.
[4]

Imiquimod (Aldara) is an immune response modifier that has been studied for the treatment of actinic cheilitis. It
promotes an immune response in the skin leading toapoptosis (death) of the tumor cells. It causes the epidermis to
be invaded by macrophages, which leads to epidermal erosion. T-cells are also activated as a result
ofimiquimod treatment. Imiquimod appears to promote an immune memory that reduces the recurrence of lesions.
There is minimal scarring. Complete clearance has been demonstrated in up to 45% of patients with actinic
keratoses. However, the dose and duration of therapy, as well as the long-term efficacy, still need to be established in
the treatment of actinic cheilitis.
[5]

Procedures[edit]
Both cryosurgery and electrosurgery are effective choices for small areas of actinic cheilitis. Cryosurgery is
accomplished by applying liquid nitrogen in an open spraying technique. Local anesthesia is not required, but
treatment of the entire lip can be quite painful. Cure rates in excess of 96% have been reported. Cryosurgeryis the
treatment of choice for focal areas of actinic cheilitis. Electrosurgery is an alternate treatment, but local anesthesia is
required, making it less practical than cryosurgery. With both techniques, adjacent tissue damage can delay healing
and promote scar formation.
[2]

More extensive or recurring areas of actinic cheilitis may be treated with either a shave vermillionectomy or a carbon
dioxide laser. The shave vemillionectomy removes a portion of the vermillion ridge but leaves the
underlying muscle intact. Considerable bleeding can occur during the procedure due to the vascular nature of the lip.
A linear scar may also form after treatment, but this can usually be minimized with massage and steroids. Healing
time is short, and effectiveness is very high.
[2]

A newer procedure uses a carbon dioxide laser to ablate the vermillion border. This treatment is relatively quick and
easy to perform, but it requires a skilled operator.Anesthesia is usually required.
Secondary infection and scarring can occur with laser ablation. In most cases, the scar is minimal, and responds well
to steroids. Pain can be a progressive problem during the healing phase, which can last three weeks or more.
However, the carbon dioxide laser also offers a very high success rate, with very few recurrences.
[2]

Chemical peeling with 50% trichloroacetic acid has also been evaluated, but results have been poor. Healing usually
takes 7-10 days with very few side effects. However, limited studies show that the success rate may be lower than
30%.
[2]

Herpes simplex
From Wikipedia, the free encyclopedia
"Herpes" redirects here. For the virus that causes herpes simplex, see Herpes simplex virus. For all types of
herpes viruses, see Herpesviridae.
Herpes simplex
Classification and external resources

Herpes labialis of the lower lip. Note the blisters in a group marked by an
arrow.
ICD-10 A60, B00, G05.1, P35.2
ICD-9 054.0, 054.1, 054.2,054.3, 771.2
DiseasesDB 5841 33021
eMedicine med/1006
MeSH D006561
Herpes simplex (Greek: herps, "creeping" or "latent") is a viral disease from the herpesviridae family
caused by both Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Infection with the herpes virus is
categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible
symptoms of which are colloquially called cold sores or fever blisters, is an infection of the face or mouth. Oral
herpes is the most common form of infection. Genital herpes, known simply as herpes, is the second most
common form of herpes. Other disorders such as herpetic whitlow, herpes gladiatorum, ocular herpes, cerebral
herpes infection encephalitis, Mollaret's meningitis,neonatal herpes, and possibly Bell's palsy are all caused by
herpes simplex viruses.
Herpes viruses cycle between periods of active diseasepresenting as blisters containing
infectious virus particlesthat last 221 days, followed by a remission period. Genital herpes, however, is
often asymptomatic, though viral shedding may still occur. After initial infection, the viruses are transported
along sensory nerves to the sensory nerve cell bodies, where they become latent and reside lifelong. Causes
of recurrence are uncertain, though some potential triggers have been identified, including immunosuppressant
drugs. The previously latent virus then multiplies new virus particles in the nerve cell and these are transported
along the axon of each neuron to the nerve terminals in the skin, where they are released. Over time, episodes
of active disease reduce in frequency and severity.
Herpes simplex is most easily transmitted by direct contact with a lesion or the body fluid of an infected
individual. Transmission may also occur through skin-to-skin contact during periods of asymptomatic shedding.
Barrier protection methods are the most reliable method of preventing transmission of herpes, but they merely
reduce rather than eliminate risk. Oral herpes is easily diagnosed if the patient presents with visible sores or
ulcers. Early stages of orofacial herpes and genital herpes are harder to diagnose; laboratory testing is usually
required.
A cure for herpes has not yet been developed. Once infected, the virus remains in the body for life. Recurrent
infections (outbreaks) may occur from time to time, especially in times of immune impairment such
as HIV and cancer-related immune suppression.
[1]
However, after several years, outbreaks become less severe
and more sporadic, and some people will become perpetually asymptomatic and will no longer experience
outbreaks, though they may still be contagious to others. Treatments with antivirals can reduce viral shedding
and alleviate the severity of symptomatic episodes. It should not be confused with conditions caused by other
viruses in the herpesviridae family such as herpes zoster, which is caused by varicella zoster virus.
The differential diagnosis includes hand, foot and mouth diseasedue to similar lesions on the skin.
Contents
[hide]
1 Classification
2 Signs and symptoms
o 2.1 Other
o 2.2 Bell's palsy
o 2.3 Alzheimer's disease
3 Pathophysiology
4 Diagnosis
5 Prevention
o 5.1 Barrier methods
o 5.2 Antivirals
o 5.3 Pregnancy
6 Treatment
o 6.1 Antiviral
o 6.2 Topical
o 6.3 Alternative medicine
7 Prognosis
8 Epidemiology
9 History
10 Society and culture
11 Research
12 References
13 External links
Classification
Herpes simplex is divided into two types: HSV type 1 and HSV type 2. HSV1 causes primarily mouth, throat,
face, eye, and central nervous system infections, whereas HSV2 causes primarily anogenital infections.
However, each may cause infections in all areas.
[2]

Signs and symptoms
HSV infection causes several distinct medical disorders. Common infection of the skin or mucosa may affect
the face and mouth (orofacial herpes), genitalia (genital herpes), or hands (herpetic whitlow). More serious
disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous
system, damaging the brain (herpes encephalitis). People with immature or suppressed immune systems, such
as newborns, transplant recipients, or people with AIDS are prone to severe complications from HSV infections.
HSV infection has also been associated with cognitive deficits of bipolar disorder,
[3]
and Alzheimer's disease,
although this is often dependent on the genetics of the infected person.
In all cases HSV is never removed from the body by the immune system. Following a primary infection, the
virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes
latent in the ganglion.
[4]
As a result of primary infection, the body produces antibodies to the particular type of
HSV involved, preventing a subsequent infection of that type at a different site. In HSV-1 infected
individuals, seroconversion after an oral infection will prevent additional HSV-1 infections such
as whitlow, genital herpes, and herpes of the eye. Prior HSV-1 seroconversion seems to reduce the symptoms
of a later HSV-2 infection, although HSV-2 can still be contracted.
Many people infected with HSV-2 display no physical symptomsindividuals with no symptoms are described
as asymptomatic or as having subclinical herpes.
[5]

Condition Description Illustration
Herpetic gingivostomatitis
Herpetic gingivostomatitis is often the initial presentation during
the first herpes infection. It is of greater severity than herpes
labialis, which is often the subsequent presentations.

Herpes labialis
Infection occurs when the virus comes into contact with oral
mucosa or abraded skin.

Herpes genitalis
When symptomatic, the typical manifestation of a primary HSV-
1 or HSV-2 genital infection is clusters of
inflamedpapules and vesicles on the outer surface of the genitals
resembling cold sores.

Herpetic whitlowand Herpes
gladiatorum
Herpes whitlow is a painful infection that typically affects the
fingers or thumbs. On occasion, infection occurs on the toes or
on the nail cuticle. Individuals that participate in contact
sports such as wrestling, rugby, and soccer sometimes acquire a
condition caused by HSV-1 known as herpes
gladiatorum, scrumpox, wrestlers herpes, or mat herpes, which
presents as skin ulceration on the face, ears, and neck.
Symptoms include fever, headache, sore throat and swollen
glands. It occasionally affects the eyes or eyelids.

Herpesviral
encephalitis andherpesviral
meningitis
A herpetic infection of the brain that is thought to be caused by
the retrograde transmission of virus from a peripheral site on
the face following HSV-1 reactivation, along the trigeminal
nerve axon, to the brain. HSV is the most common cause of viral
encephalitis. When infecting the brain, the virus shows a
preference for the temporal lobe.
[6]
HSV-2 is the most common
cause of Mollaret's meningitis, a type of recurrent viral
meningitis.

Herpes esophagitis
Symptoms may include painful swallowing (odynophagia) and
difficulty swallowing (dysphagia). It is often associated with
impaired immune function
(e.g. HIV/AIDS, immunosuppression in solid organ transplants).

Other
Neonatal herpes simplex is a HSV infection in an infant. It is a rare but serious condition, usually caused
by vertical transmission of HSV (type 1 or 2) from mother to newborn. During immunodeficiency herpes simplex
can cause unusual lesions in the skin. One of the most striking is the appearance of clean linear erosions in
skin creases, with the appearance of a knife cut.
[7]
Herpetic sycosis is a recurrent or initial herpes simplex
infection affecting primarily the hair follicle.
[8]:369
Eczema herpeticum is an infection with herpesvirus in patients
with chronic atopic dermatitis may result in spread of herpes simples throughout the eczematous
areas.
[8]:373
Herpetic keratoconjunctivitis is a primary infection typically presents as swelling of
the conjunctiva and eyelids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of
the cornea.
Bell's palsy
Although the exact cause of Bell's palsy, a type of facial paralysis, is unknown it may be related to reactivation
of herpes simplex virus type 1.
[9]
This theory has been contested, however, since HSV is detected in large
numbers of individuals having never experienced facial paralysis, and higher levels of antibodies for HSV are
not found in HSV-infected individuals with Bell's palsy compared to those without.
[10]
Regardless antivirals have
been found to not improve outcomes.
[11]

Alzheimer's disease
HSV-1 has been proposed as a possible cause of Alzheimer's disease.
[12][13]
In the presence of a certain gene
variation (APOE-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system
and increases ones risk of developing Alzheimers disease. The virus interacts with the components and
receptors of lipoproteins, which may lead to the development of Alzheimer's disease.
[14][15]

Pathophysiology
Herpes Shedding
[16]

HSV-2 genital 1525% of days
HSV-1 oral 633% of days
HSV-1 genital 5% of days
HSV-2 oral 1% of days
Herpes is contracted through direct contact with an active lesion or body fluid of an infected person.
[17]
Herpes
transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can
pass the virus to an HSV seronegative person. Herpes simplex virus 2 is typically contracted through direct
skin-to-skin contact with an infected individual but can also be contacted via exposure to infected saliva,
semen, vaginal fluid or the fluid from herpetic blisters.
[18]
To infect a new individual, HSV travels through tiny
breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on
mucous membranes are sufficient to allow viral entry.
HSV asymptomatic shedding occurs at some time in most individuals infected with herpes. It can occur more
than a week before or after a symptomatic recurrence in 50% of cases.
[19]
Virus enters into susceptible cells via
entry receptors
[20]
such as nectin-1, HVEM and 3-O sulfated heparan sulfate.
[21]
Infected people that show no
visible symptoms may still shed and transmit virus through their skin; asymptomatic shedding may represent
the most common form of HSV-2 transmission.
[19]
Asymptomatic shedding is more frequent within the first 12
months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic
shedding.
[22]
There are indications that some individuals may have much lower patterns of shedding, but
evidence supporting this is not fully verified; no significant differences are seen in the frequency of
asymptomatic shedding when comparing persons with one to twelve annual recurrences to those with no
recurrences.
[19]

Antibodies that develop following an initial infection with a type of HSV prevents reinfection with the same virus
typea person with a history of orofacial infection caused by HSV-1 cannot contract herpes whitlow or a
genital infection caused by HSV-1.
[citation needed]
In a monogamous couple, a seronegative female runs a greater
than 30% per year risk of contracting an HSV infection from a seropositive male partner.
[23]
If an oral HSV-1
infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies
against a future genital HSV-1 infection. Herpes simplex is a double stranded DNA virus.
[24]

Diagnosis
Primary orofacial herpes is readily identified by clinical examination of persons with no previous history of
lesions and contact with an individual with known HSV-1 infection. The appearance and distribution of sores in
these individuals typically presents as multiple, round, superficial oral ulcers, accompanied by
acute gingivitis.
[25]
Adults with non-typical presentation are more difficult to diagnose. Prodromal symptoms that
occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of
other disorders, such as allergic stomatitis. When lesions do not appear inside the mouth, primary orofacial
herpes is sometimes mistaken for impetigo, a bacterial infection. Common mouth ulcers (aphthous ulcer) also
resemble intraoral herpes, but do not present a vesicularstage.
[25]

Genital herpes can be more difficult to diagnose than oral herpes, since most HSV-2-infected persons have no
classical symptoms.
[25]
Further confusing diagnosis, several other conditions resemble genital herpes,
including fungal infection, lichen planus, atopic dermatitis, and urethritis.
[25]
Laboratory testing is often used to
confirm a diagnosis of genital herpes. Laboratory tests include: culture of the virus, direct fluorescent
antibody (DFA) studies to detect virus, skin biopsy, andpolymerase chain reaction (PCR) to test for presence of
viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and
time constraints discourage their regular use in clinical practice.
[25]

Until recently, serological tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in
clinical practice.
[25]
The older IgM serologic assay could not differentiate between antibodies generated in
response to HSV-1 or HSV-2 infection. However, the new Immunodot glycoprotein G-specific (IgG) HSV test is
more than 98% specific at discriminating HSV-1 from HSV-2.
[26]
It is the opinion of some modern medical
professionals that the new IgG test should always be clinically preferred to the old IgM test, however not all
doctors appear to be informed of the availability of the newer, reliable IgG tests.
[27]

Prevention


Barrier protection, such as a condom, can reduce the risk of herpes transmission.
As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than
men.
[28]
On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from
infected male to female is approximately 811%.
[23][29]
This is believed to be due to the increased exposure of
mucosal tissue to potential infection sites. Transmission risk from infected female to male is approximately 4
5% annually.
[29]
Suppressive antiviral therapy reduces these risks by 50%.
[30]
Antivirals also help prevent the
development of symptomatic HSV in infection scenariosmeaning the infected partner will be seropositive but
symptom freeby about 50%. Condom use also reduces the transmission risk significantly.
[31][32]
Condom use
is much more effective at preventing male to female transmission than vice-versa.
[31]
The effects of combining
antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in
annual transmission risk.
[citation needed]
These figures reflect experiences with subjects having frequently recurring
genital herpes (>6 recurrences per year). Subjects with low recurrence rates and those with no clinical
manifestations were excluded from these studies.
[citation needed]
Previous HSV-1 infection appears to reduce the
risk for acquisition of HSV-2 infection among women by a factor of 3.
[33]

However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom a
person will have of their own infection is the horizontal transmission to a sexual partner or the vertical
transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of
their infection, they are considered at high risk for spreading HSV.
[citation needed]

In October 2011, it was reported that the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal
gel, reduced herpes virus sexual transmission by 51%.
[34]

Barrier methods
Condoms offer moderate protection against HSV-2 in both men and women, with consistent condom users
having a 30% lower risk of HSV-2 acquisition compared with those that never use condoms.
[35]
A female
condom can provide greater protection than the male condom, as it covers the labia.
[36]
The virus cannot pass
through a synthetic condom, but a male condom's effectiveness is limited
[37]
because herpes ulcers may
appear on areas not covered by the male condom. Neither type of condom prevents contact with the scrotum,
anus, buttocks, or upper thighs, areas that may come in contact with ulcers or genital secretions during sexual
activity. Protection against herpes simplex depends on the site of the ulcer; therefore if ulcers appear on areas
not covered by condoms, abstaining from sexual activity until the ulcers are fully healed is one way to limit risk
of transmission.
[38]
The risk is not eliminated, however, as viral shedding capable of transmitting infection may
still occur while the infected partner is asymptomatic.
[39]
The use of condoms or dental dams also limits the
transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex.
When one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such
asvalaciclovir, in conjunction with a condom further decreases the chances of transmission to the uninfected
partner.
[4]
Topical microbicides that contain chemicals that directly inactivate the virus and block viral entry are
being investigated.
[4]

Antivirals
Antivirals may reduce asymptomatic shedding; it is believed asymptomatic genital HSV-2 viral shedding occurs
on 20% of days per year in patients not undergoing antiviral treatment, versus 10% of days while on antiviral
therapy.
[19]

Pregnancy
The risk of transmission from mother to baby is highest if the mother becomes infected at around the time of
delivery (30% to 60%),
[40][41]
since insufficient time will have occurred for the generation and transfer of
protective maternal antibodies before the birth of the child. In contrast, the risk falls to 3% if it is a recurrent
infection,
[42]
and is 13% is the woman seropositive for both HSV-1 and HSV-2,
[42][43]
and is less than 1% if there
are no visible lesions.
[42]
Women seropositive for only one type of HSV are only half as likely to transmit HSV as
infected seronegative mothers. To prevent neonatal infections, seronegative women are recommended to
avoid unprotected oral-genital contact with an HSV-1 seropositive partner and conventional sex with a partner
having a genital infection during the last trimester of pregnancy. Mothers infected with HSV are advised to
avoid procedures that would cause trauma to the infant during birth (e.g. fetal scalp electrodes, forceps, and
vacuum extractors) and, should lesions be present, to elect caesarean section to reduce exposure of the child
to infected secretions in the birth canal.
[4]
The use of antiviral treatments, such as acyclovir, given from the 36th
week of pregnancy, limits HSV recurrence and shedding during childbirth, thereby reducing the need for
caesarean section.
[4]

Acyclovir is the recommended antiviral for herpes suppressive therapy during the last months of pregnancy.
The use of valaciclovir and famciclovir, while potentially improving compliance have less well determined safety
in pregnancy.
Treatment
There is no method to eradicate herpes virus from the body, but antiviral medications can reduce the
frequency, duration, and severity of outbreaks. Analgesics such as ibuprofen and acetaminophen can reduce
pain and fever. Topical anesthetic treatments such as prilocaine, lidocaine, benzocaine or tetracaine can also
relieve itching and pain.
[44][45][46]

Antiviral


The antiviral medication acyclovir
There are several antivirals that are effective for treating herpes
including: aciclovir (acyclovir), valaciclovir (valacyclovir),famciclovir, and penciclovir. Aciclovir was the first
discovered and is now available in generic.
[47]
Valacyclovir is also available as a generic.
[48]

Evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis
[49]
as well as herpes
infections in people with cancer.
[50]
The evidence to support the use of acyclovir in primary herpetic
gingivostomatitis is less strong.
[51]

Topical
A number of topical antivirals are effective for herpes labialis including acyclovir, penciclovir,
and docosanol.
[49][52]

Alternative medicine
Certain dietary supplements and alternative remedies are claimed to be beneficial in the treatment of
herpes.
[53]
There is however insufficient evidence to support use of many of these compounds
including echinacea, eleuthero, L-lysine, zinc,monolaurin bee products and aloe vera.
[54]
While there are a
number of small studies showing possible benefit from monolaurin, L-lysine, aspirin, lemon balm, topical zinc or
licorice root cream in treatment, these are preliminary studies that have not been confirmed by higher
qualityrandomized controlled studies.
[55]

Prognosis
Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the
nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of
the nucleus of a nerve's cell body. HSV latency is staticno virus is producedand is controlled by a number
of viral genes, including Latency Associated Transcript (LAT).
[56]

Many HSV-infected people experience recurrence within the first year of infection.
[4]
Prodrome precedes
development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where
lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours
before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the
appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop,
lesions are less painful and heal faster (within 510 days without antiviral treatment) than those occurring
during the primary infection.
[4]
Subsequent outbreaks tend to be periodic or episodic, occurring on average four
to five times a year when not using antiviral therapy.
The causes of reactivation are uncertain, but several potential triggers have been documented. A recent study
(2009) showed that the protein VP16 plays a key role in reactivation of the dormant virus.
[57]
Changes in the
immune system during menstruation may play a role in HSV-1 reactivation.
[58][59]
Concurrent infections, such as
viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to
infection is the likely source of the historic terms cold sore andfever blister.
Other identified triggers include: local injury to the face, lips, eyes, or mouth, trauma, surgery, radiotherapy, and
exposure to wind, ultraviolet light, or sunlight.
[60][61][62][63][64]

The frequency and severity of recurrent outbreaks vary greatly between people. Some individuals' outbreaks
can be quite debilitating with large, painful lesions persisting for several weeks, while others will experience
only minor itching or burning for a few days. There is some evidence that genetics plays a role in the frequency
of cold sore outbreaks. An area of human chromosome 21 that includes 6 genes has been linked to frequent
oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals will experience
fewer outbreaks and outbreak symptoms will often become less severe. After several years, some people will
become perpetually asymptomatic and will no longer experience outbreaks, though they may still be contagious
to others. Immuno-compromised individuals may experience episodes that are longer, more frequent, and more
severe. Antiviral medication has been proven to shorten the frequency and duration of outbreaks.
[65]
Outbreaks
may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected
ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of
the spine, the buttocks, or the back of the thighs. HSV-2 infected individuals are at higher risk for
acquiring HIV when practicing unprotected sex with HIV-positive persons, in particular during an outbreak with
active lesions.
[66]

Epidemiology
Main article: Epidemiology of herpes simplex
Worldwide rates of either HSV-1 and/or HSV-2 are between 60-95% in adults.
[2]
HSV1 is more common than
HSV2 with rates of both increasing as people age.
[2]
HSV-1 rates are between 70% to 80% in populations of low
socio-economic status and 40% to 60% in populations of improved socio-economic status.
[2]
Prevalence of
HSV-2 is those between the ages of 15 and 50 is approximately 535 million as of 2003 or 16% of the
population with greater rates among women and in those in the developing world.
[67]
Rates of infection are
determined by the presence of antibodies against either viral species.
[68]

An estimated 536 million people worldwide were infected with HSV-2 in 2003, with the highest rates in sub-
Saharan Africa and the lowest rates in western Europe.
[69]

In the US, 57.7% of the population is infected with HSV-1
[70]
and 16.2% are infected with HSV-2. Among those
HSV-2 seropositive, only 18.9% were aware that they were infected.
[71]
During 20052008, the prevalence of
HSV-2 was 39.2% in blacks and 20.9% in women.
[72]

History
Herpes has been known for at least 2,000 years. It is said that Emperor Tiberius banned kissing in Rome for a
time due to so many people having cold sores. In the 16th century Romeo and Juliet, it is mentioned that there
are blisters "o'er ladies' lips." In 18th century it was so common among prostitutes that it was called "a
vocational disease of women."
[73]
The term Herpes Simplex appeared in Richard Boulton's A System of
Rational and Practical Chirurgery in 1713, where the termsHerpes miliaris and Herpes exedens also appeared.
Herpes was not found to be a virus until the 1940s.
[73]

Herpes antiviral therapy began in the early 1960s with the experimental use of medication that interfered with
viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or
debilitating illness such as adult encephalitis,
[74]
keratitis,
[75]
in immunocompromised (transplant) patients,
[76]
or
disseminated herpes zoster.
[77]
The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine,
IUdR, or(IDU) and 1--D-arabinofuranosylcytosine or ara-C,
[78]
later marketed under the name cytosar or
cytorabine. The usage expanded to include topical treatment of herpes simplex,
[79]
zoster, and
varicella.
[80]
Some trials combined different antivirals with differing results.
[74]
The introduction of 9--D-
arabinofuranosyladenine, AKA ara-A or vidarabine, considerably less toxic than Ara-C, in the mid-1970s,
heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically
administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for
the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the U.S.
Food and Drug Administration (FDA) in 1977. Other experimental antivirals of that period included:
Heparin,
[81]
trifluorothymidine (TFT),
[82]
Ribivarin,
[83]
interferon,
[84]
Virazole,
[85]
and 5-methoxymethyl-2'-
deoxyuridine (MMUdR).
[86]
The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA acyclovir, in the late
1970s
[87]
raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late
1980s.
[88]
The lower toxicity and ease of administration over vidarabine has led to acyclovir becoming the drug
of choice for herpes treatment after it was licensed by the FDA in 1998.
[89]
Another advantage in the treatment
of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, something
that did not occur when compared with increased dosages of vidarabine.
[89]
On the other side of the equation,
acyclovir seems to inhibit antibody response and newborns on acyclovir antiviral treatment experienced a
slower rise in antibody titer than those on vidarabine.
[89]

Society and culture
Herpes simplex was not always stigmatised. It was merely a cold sore in an unusual place until the 1970s. As
late as 1975, a study of "Psychological morbidity in a clinic for sexually transmitted disease does not mention
herpes simplex because at that time, there was no significant morbidity problem (i.e. mental anxiety or illness)
associated with the virus.
[90]

Pedro Cuatrecasas states, "during the R&D of acyclovir (Zovirax), marketing [department of Burroughs
Wellcome] insisted that there were 'no markets for this compound. Most had hardly heard of genital herpes...
Thus marketing the medical condition separating the 'normal cold sore from the 'stigmatized genital infection
was to become the key to marketing the drug, a process now known as 'disease mongering.
[91][92]

Since the creation of the herpes hype, some people experience negative feelings related to the condition
following diagnosis, in particular if they have acquired the genital form of the disease. Feelings can
include depression, fear of rejection, feelings of isolation, fear of being found out, and self-destructive
feelings.
[93]
These feelings usually lessen over time. Much of the hysteria and stigma surrounding herpes stems
from a media campaign beginning in the late 1970s and peaking in the early 1980s. There were multiple
articles worded in fear-mongering and anxiety-provoking terminology, such as the now ubiquitous "attacks,"
"outbreaks," "victims," and "sufferers." At one point the term "herpetic" even entered the popular lexicon. The
articles were published by Reader's Digest, U.S. News, and Time magazine, among others. A made-for-TV
movie was named Intimate Agony. The peak was when Time magazine had 'Herpes: The New Scarlet Letter'
on the cover in August 1982, forever stigmatizing the word in the public mind.
[73]
Herpes support groups have
been formed in the United States and the UK, providing information about herpes and running message forums
and dating websites for sufferers. People with the herpes virus are often hesitant to divulge to other people,
including friends and family, that they are infected. This is especially true of new or potential sexual partners
whom they consider casual.
[94]

Research
Main article: Herpes simplex research
Researchers at the University of Florida have made a Hammerhead ribozyme that targets and cleaves the
mRNA of essential genes in HSV-1. The hammerhead, which targets the mRNA of the UL20 gene, greatly
reduced the level of HSV-1 ocular infection in rabbits, and reduced the viral yield in vivo.
[95]
The gene-targeting
approach uses a specially designed RNA enzyme to inhibit strains of the herpes simplex virus. The enzyme
disables a gene responsible for producing a protein involved in the maturation and release of viral particles in
an infected cell. The technique appears to be effective in experiments with mice and rabbits, but further
research is required before it can be attempted in people infected with herpes.
[96]

Another possibility to eradicate the HSV-1 variant is being pursued by a team at Duke University. By figuring
out how to switch all copies of the virus in the host from latency to their active stage at the same time, rather
than the way the virus copies normally stagger their activity stage, leaving some dormant somewhere at all
times, it is thought that conventional anti-viral drugs can kill the entire virus population completely, since they
can no longer hide in the nerve cells. One class of drugs calledantagomir could serve this purpose. These are
chemically engineered oligonucleotides or short segments of RNA, that can be made to mirror their target
genetic material, namely herpes microRNAs. They could be engineered to attach and thus 'silence' the
microRNA, thus rendering the virus incapable of remaining latent in its host.
[97]
Professor Cullen believes a drug
could be developed to block the microRNA whose job it is to suppress HSV-1 into latency.
[98]

A chancre (/kr/ SHANG-kr)
[1]
is a painless ulceration (sore) most commonly formed during the primary stage
ofsyphilis. This infectious lesion forms approximately 21 days after the initial exposure to Treponema pallidum,
the gram-negative spirochaete bacterium yielding syphilis. Chancres transmit the sexually transmissible disease
of syphilis through direct physical contact. These ulcers usually form on or around the anus, mouth, penis,
and vagina. Chancres may diminish between three to six weeks without the application of medication.
In addition, chancres as well as a painless ulceration formed during the primary stage of syphilis, are associated with
theAfrican trypanosomiasis sleeping sickness, surrounding the area of the tsetse fly bite.
Contents
[hide]
1 Etymology
2 Similarities with chancroid
3 Differences from chancroid
4 See also
5 References
Etymology[edit|edit source]
The word "chancre" (French pronunciation: ) means "little ulcer" in Old French. Related to the English "canker",
they both come from the Latin cancer, meaningcrab,
[2]
which is a translation from the Greek word "
(karknos)", also meaning crab.
[3]

Similarities with chancroid[edit]
Similarities between the conditions chancre and chancroid:
Both originate as pustules at the site of inoculation, and progress to ulcerated lesions
Both lesions are typically 12 cm in diameter
Both lesions are caused by sexually transmissible organisms
Both lesions typically appear on the genitals of infected individuals


Candidiasis
From Wikipedia, the free encyclopedia
"Thrush (infection)" redirects here. For the hoof infection, see Thrush (horse).
Candidiasis
Classification and external resources

Oral candidiasis (thrush)
ICD-10 B37
ICD-9 112
DiseasesDB 1929
MedlinePlus 001511
eMedicine med/264 emerg/76ped/312 derm/67
MeSH D002177
Candidiasis or thrush is a fungal infection (mycosis) of any of the Candida species (all yeasts), of
which Candida albicans is the most common.
[1][2]
Also commonly referred to as a yeast infection, candidiasis
is also technically known as candidosis, moniliasis, and oidiomycosis.
[3]

Candidiasis encompasses infections that range from superficial, such as oral thrush and vaginitis,
to systemic and potentially life-threatening diseases. Candida infections of the latter category are also referred
to as candidemia and are usually confined to severely immunocompromised persons, such
as cancer, transplant, and AIDS patients, as well as nontrauma emergency surgery patients.
[4]

Superficial infections of skin and mucosal membranes by Candida causing
local inflammation and discomfort are common in many human populations.
[2][5][6]
While clearly attributable to
the presence of the opportunistic pathogens of the genus Candida, candidiasis describes a number of different
disease syndromes that often differ in their causes and outcomes.
[2][5]

Contents
[hide]
1 Classification
2 Signs and symptoms
3 Causes
4 Diagnosis
5 Treatment
o 5.1 Localized infection
o 5.2 Blood infection
6 History
7 Society and culture
8 References
9 External links
Classification
Candidiasis may be divided into the following types:
[3]

Angular cheilitis (perlche)
Antibiotic candidiasis (iatrogenic candidiasis)
Candidal intertrigo
Candidal paronychia
Candidal vulvovaginitis (vaginal yeast infection)
Candidid
Chronic mucocutaneous candidiasis
Congenital cutaneous candidiasis
Diaper candidiasis
Erosio interdigitalis blastomycetica
Oral candidiasis (thrush)
Perianal candidiasis
Systemic candidiasis
Signs and symptoms


Skin candidiasis


Nail candidiasis (onychomycosis)
Symptoms of candidiasis vary depending on the area affected.
[7]
Most candidial infections result in minimal
complications such as redness, itching and discomfort, though complications may be severe or even fatal if left
untreated in certain populations. In immunocompetent persons, candidiasis is usually a very localized infection
of the skin or mucosal membranes, including the oral cavity (thrush), the pharynx or esophagus,
the gastrointestinal tract, the urinary bladder, or the genitalia (vagina, penis).
[1]

Candidiasis is a very common cause of vaginal irritation, or vaginitis, and can also occur on the male genitals.
Inimmunocompromised patients, Candida infections can affect the esophagus with the potential of
becoming systemic, causing a much more serious condition, a fungemia called candidemia.
[5][6]

Thrush is commonly seen in infants. It is not considered abnormal in infants unless it lasts longer than a few
weeks.
[8]

Infection of the vagina or vulva may cause severe itching, burning, soreness, irritation, and a whitish or whitish-
graycottage cheese-like discharge, often with a curd-like appearance. These symptoms are also present in the
more common bacterial vaginosis.
[9]
In a 2002 study published in the Journal of Obstetrics and Gynecology,
only 33% of women who were self-treating for a yeast infection actually had a yeast infection, while most had
either bacterial vaginosis or a mixed-type infection.
[10]
Symptoms of infection of the male genitalia include red,
patchy sores near the head of the penis or on the foreskin, severe itching, or a burning sensation. Candidiasis
of the penis can also have a white discharge, although uncommon.
[citation needed]

Causes
See also: Candida albicans
Candida yeasts are generally present in healthy humans, particularly on the skin, but their growth is normally
limited by the human immune system, by competition of other microorganisms, such as bacteria occupying the
same locations in the human body,
[11]
and in the case of skin, by the relative dryness of the skin,
as Candida requires moisture for growth.
[12]

C. albicans was isolated from the vaginas of 19% of apparently healthy women, i.e., those who experienced
few or no symptoms of infection. External use of detergents or douches or internal disturbances (hormonal or
physiological) canperturb the normal vaginal flora, consisting of lactic acid bacteria, such as lactobacilli, and
result in an overgrowth ofCandida cells, causing symptoms of infection, such as
local inflammation.
[13]
Pregnancy and the use of oral contraceptives have been reported as risk
factors.
[14]
Diabetes mellitus and the use of antibacterial antibiotics are also linked to an increased incidence of
yeast infections.
[14]
Diets high in simple carbohydrates have been found to affect rates of oral
candidiases,
[15]
and hormone replacement therapy and infertility treatments may also be predisposing
factors.
[16]
Wearing wet swimwear for long periods of time is also believed to be a risk factor.
[2]

A weakened or undeveloped immune system or metabolic illnesses such as diabetes are significant
predisposing factors of candidiasis.
[17]
Diseases or conditions linked to candidiasis
include HIV/AIDS, mononucleosis, cancer treatments, steroids, stress, and nutrient deficiency. Almost 15% of
people with weakened immune systems develop a systemic illness caused by Candida species.
[18]
In extreme
cases, these superficial infections of the skin or mucous membranes may enter into the bloodstream and cause
systemic Candida infections.
In penile candidiasis, the causes include sexual intercourse with an infected individual, low immunity,
antibiotics, and diabetes. Male genital yeast infections are less common, and incidences of infection are only a
fraction of those in women; however, yeast infection on the penis from direct contact via sexual intercourse with
an infected partner is not uncommon.
[19]

Candida species are frequently part of the human body's normal oral and intestinal flora. Treatment
with antibiotics can lead to eliminating the yeast's natural competitors for resources, and increase the severity
of the condition.
[20]
Higher prevalence of colonization of C. albicans was reported in young individuals
with tonguepiercing, in comparison to unpierced matched individuals.
[21]
In the Western Hemisphere, about
75% of females are affected at some time in their lives.
Diagnosis


Agar plate culture of C. albicans


Micrograph of esophageal candidiasis showing hyphae, biopsy specimen, PAS stain
Diagnosis of a yeast infection is done either via microscopic examination or culturing.
For identification by light microscopy, a scraping or swab of the affected area is placed on a microscope slide.
A single drop of 10% potassium hydroxide (KOH) solution is then added to the specimen. The KOH dissolves
the skin cells, but leaves the Candida cells intact, permitting visualization of pseudohyphae and budding yeast
cells typical of manyCandida species.
For the culturing method, a sterile swab is rubbed on the infected skin surface. The swab is then streaked on a
culture medium. The culture is incubated at 37C for several days, to allow development of yeast or bacterial
colonies. The characteristics (such as morphology and colour) of the colonies may allow initial diagnosis of the
organism causing disease symptoms.
[22]

Treatment
Candidiasis is commonly treated with antimycotics; these antifungal drugs include topical clotrimazole,
topical nystatin,fluconazole, and topical ketoconazole.
Localized infection
A one-time dose of fluconazole is 90% effective in treating a vaginal yeast infection.
[23]
Local treatment may
include vaginal suppositories or medicated douches. Other types of yeast infections require different
dosing. Gentian violet can be used for thrush in breastfeeding babies, but when used in large quantities, it can
cause mouth and throat ulcerations, and has been linked to mouth cancer in humans and to cancer in the
digestive tract of other animals.
[24]
C. albicans can develop resistance to fluconazole, this being more of an
issue in those with HIV/AIDS who are often treated with multiple courses of fluconazole for recurrent oral
infections.
[25]

There is not enough evidence to determine if probiotics (either as pills or as yogurt) has an effect on the rate of
occurrence of vaginal yeast infections.
[26]
No benefit has been found for active infections.
[27]

Blood infection
In candidial infections of the blood intravenous fluconazole or an echinocandin such as caspofungin may be
used.
[28]
Amphotericin B is another option.
[28]

History
Descriptions of what sounds like oral thrush go back to the time of Hippocrates circa 460 - 370 BC.
[7]

The genus Candida and species C. albicans were described by botanist Christine Marie Berkhout in her
doctoral thesis at the University of Utrecht in 1923. Over the years, the classification of the genera and species
has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been
known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum,
which means the name is authorized for use by the International Botanical Congress (IBC).
[29]

The genus Candida includes about 150 different species; however, only a few are known to cause human
infections. C. albicans is the most significant pathogenicspecies. Other species pathogenic in humans
include C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, and C. lusitaniae.
Society and culture
Some alternative medicine proponents postulate a widespread occurrence of systemic candidiasis (or candida
hypersensitivity syndrome, yeast allergy, fungal type dysbiosis or gastrointestinal candida overgrowth), a
medically unrecognised condition.
[30]
The view was most widely promoted in a book published by Dr. William
Crook
[31]
that hypothesized a variety of common symptoms such as fatigue, PMS, sexual
dysfunction, asthma, psoriasis, digestive and urinary problems, multiple sclerosis, and muscle pain could be
caused by subclinical infections of C. albicans.
[31]
Crook suggested a variety of remedies to treat these
symptoms, including dietary modification (commonly referred to as the rainbow dieteating fresh foods and
avoiding foods high in vinegar, sugar, or yeast), prescription antifungals, pau d'arco tea, echinacea tea,
and colonic irrigation. With the exception of the few dietary studies in the urinary tract infection section,
conventional medicine has not used most of these alternatives, since there is limited scientific evidence proving
either their effectiveness or that subclinical systemic candidiasis is a viable diagnosis.
[32][33][34][35]

In 1990, alternative health vendor Nature's Way signed an FTC consent agreement not to misrepresent in
advertising any self-diagnostic test concerning yeast conditions or to make any unsubstantiated representation
concerning any food or supplement's ability to control yeast conditions, with a fine of $30,000 payable to the
National Institutes of Health for research in genuine candidiasis.
[30]

Allergic contact dermatitis
From Wikipedia, the free encyclopedia
Allergic contact dermatitis
Classification and external resources
ICD-10 L23
ICD-9 692
DiseasesDB 29435
MeSH D017449
Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic
response caused by contact with a substance; the other type being irritant contact dermatitis (ICD).
Although less common than ICD, ACD is accepted to be the most prevalent form of immunotoxicity found in
humans.
[1]
By its allergic nature, this form of contact dermatitis is a hypersensitive reaction that is atypical within
the population. The mechanisms by which these reactions occur are complex, with many levels of fine control.
Their immunology centres around the interaction of immunoregulatory cytokines and discrete subpopulations of
T lymphocytes.
Contents
[hide]
1 Pathophysiology
2 Allergens
3 Symptoms
4 Treatment
5 Diagnosis
6 See also
7 References
8 Further reading
Pathophysiology[edit]
ACD arises as a result of two essential stages: an induction phase, which primes and sensitizes the immune
system for an allergic response, and an elicitation phase, in which this response is triggered (Kimble et al.
2002). As such, ACD is termed a Type IV delayed hypersensitivity reaction involving a cell-mediated allergic
response. Contact allergens are essentially soluble haptens (low in molecular weight) and, as such, have the
physico-chemical properties that allow them to cross the stratum corneum of the skin. They can only cause
their response as part of a complete antigen, involving their association with epidermal proteins forming
hapten-protein conjugates. This, in turn, requires them to be protein-reactive.
The conjugate formed is then recognized as a foreign body by the Langerhans cells (LCs) (and in some cases
other Dendritic cells (DCs)), which then internalize the protein; transport it via the lymphatic system to the
regional lymph nodes; and present the antigen to T-lymphocytes. This process is controlled by cytokines and
chemokines - with tumor necrosis factor alpha (TNF-) and certain members of the interleukin family (1, 13 and
18) - and their action serves either to promote or to inhibit the mobilization and migration of these LCs. (Kimble
et al. 2002) As the LCs are transported to the lymph nodes, they become differentiated and transform into DCs,
which are immunostimulatory in nature.
Once within the lymph glands, the differentiated DCs present the allergenic epitope associated with the
allergen to T lymphocytes. These T cells then divide and differentiate, clonally multiplying so that if the allergen
is experienced again by the individual, these T cells will respond more quickly and more aggressively.
White et al. have suggested that there appears to be a threshold to the mechanisms of allergic sensitisation by
ACD-associated allergens (1986).
[2]
This is thought to be linked to the level at which the toxin induces the up-
regulation of the required mandatory cytokines and chemokines. It has also been proposed that the vehicle in
which the allergen reaches the skin could take some responsibility in the sensitisation of the epidermis by both
assisting the percutaneous penetration and causing some form of trauma and mobilization of cytokines itself.
Allergens[edit]
Common allergens implicated include the following:
Nickel (nickel sulfate hexahydrate) - metal frequently encountered in jewelry and clasps or buttons on
clothing
Gold (gold sodium thiosulfate) - precious metal often found in jewelry and dental materials
Balsam of Peru (Myroxylon pereirae) - a fragrance used in perfumes and skin lotions, derived from tree
resin (see also Tolu balsam). It may also be a component of artificial vanilla and/or cinnamon flavorings.
Chromium - used in the tanning of leather. Also a component of uncured cement/mortar, facial cosmetics
and some bar soaps.
Oily coating from plants of the Toxicodendron genus: poison ivy, poison oak, and poison sumac.
Thimerosal - a mercury compound used in local antiseptics and in vaccines
Neomycin - a topical antibiotic common in first aid creams and ointments, cosmetics, deodorant, soap and
pet food. Found by itself, or in Neosporin or Triple Antibiotic
Fragrance mix - a group of the eight most common fragrance allergens found in foods, cosmetic products,
insecticides, antiseptics, soaps, perfumes and dental products
[3]

Formaldehyde - a preservative with multiple uses, e.g., in paper products, paints, medications, household
cleaners, cosmetic products and fabric finishes. Often released into products by the use of formaldehyde
releasers such as imidazolidinyl urea, diazolidinyl urea, Quaternium-15, DMDM Hydantoin and 2-bromo-2-
nitropropane-1,3-diol.
Cobalt chloride - metal found in medical products; hair dye; antiperspirant; metal-plated objects such as
snaps, buttons or tools; and in cobalt blue pigment
Bacitracin - a topical antibiotic found by itself, or as Polysporin or Triple Antibiotic
Quaternium-15 - preservative in cosmetic products (self-tanners, shampoo, nail polish, sunscreen) and in
industrial products (polishes, paints and waxes).
[4]

Colophony (Rosin) - Rosin, sap or sawdust typically from spruce or fir trees
Topical steroid - see steroid allergy
Photographic developers, especially those containing metol
Topical anesthetics such as pramoxine or diphenhydramine, after prolonged use
Methylchloroisothiazolinone/Methylisothiazolinone is a preservative used in wash-off products such as
shampoos/conditioners.
Symptoms[edit]
The symptoms of allergic contact dermatitis are very similar to the ones caused by irritant contact dermatitis,
which makes the first even harder to diagnose. The first sign of allergic contact dermatitis is the presence of the
rash or skin lesion at the site of exposure.
[5]
Depending on the type of allergen causing it, the rash can ooze,
drain or crust and it can become raw, scaled or thickened. Also, it is possible that the skin lesion does not take
the form of a rash but it may include papules, blisters,vesicles or even a simple red area. The main difference
between the rash caused by allergic contact dermatitis and the one caused by irritant contact dermatitis is that
the first one tends to be confined to the area where the trigger touched the skin, whereas in the second case,
the rash is more likely to be more widespread on the skin.
[6]
Another characteristic of the allergic contact
dermatitis rash is that it usually appears after a day or two after exposure to the allergen, unlike irritant contact
dermatitis that appears immediately after the contact with the trigger.
Other symptoms may include itching, skin redness or inflammation, localized swelling and the area may
become more tender or warmer. If left untreated, the skin may darken and become leathery and
cracked.
[7]
Pain can also be present.
The symptoms of allergic contact may persist for as long as one month before resolving completely. Once an
individual has developed a skin reaction to a certain substance it is most likely that they will have it for the rest
of their life, and the symptoms will reappear when in contact with the allergen.
Treatment[edit]
Persons who develop the rash and the other symptoms from a certain trigger are most likely to have it for the
rest of their lives and detecting and avoiding the allergen is mandatory in treating the condition and resolving its
symptoms.
The first step in treating the condition is applying a damp cloth shortly after the skin problem first shows to
make sure that all of the irritant has been removed from the area.
[8]
In some cases, the best treatment is to do
nothing to the area.
[5]

In mild to moderate cases, patients may use skin creams containing corticosteroids to reduce the inflammation.
These creams should be used carefully and according to the instructions they come with because when
overused over longer periods of time they can cause serious skin conditions. Also, calamine lotion and
cool oatmealbaths may relieve itching.
[9]
Over the counter diphenhydramine by mouth is helpful for night time
itching.
Usually, severe cases are treated with systemic corticosteroids which may be tapered gradually, with various
dosing schedules ranging from a total of 12 20 days to prevent the recurrence of the rash as well as a topical
corticosteroid.
[5]
Tacrolimus ointment or pimecrolimus cream can also be used additionally to the corticosteroid
creams or instead of these. Oral antihistamines such as diphenhydramine or hydroxyzine may also be used in
more severe cases to relieve the intense itching. Topical antihistamines are not advised as there might be a
second skin reactions from the lotion itself.
The other symptoms caused by allergic contact dermatitis are generally eased with wet dressings and drying
lotions to stop the itching. In most cases however, medication or actual treatment is not required as long as the
trigger has been identified and avoided. The discomfort caused by the symptoms may be relieved by wearing
smooth-textured clothing to avoid more skin irritation or by avoiding soaps with perfumes and dyes.
Commonly, the symptoms may resolve without treatment in 2 to 4 weeks but specific medication may hasten
the healing as long as the trigger is avoided. Also, the condition might become chronic if the allergen is not
detected and therefore it is not avoided.
Frequent moisturizing (and after every time you wash your hands) with organic coconut oil has found to
completely cure symptoms in many sufferers.
Avoiding foods with high sources of nickel have also been found to help, particular dark chocolate, which is
particularly high in nickel, as are many nuts, grains and pulses.
Diagnosis[edit]
Diagnosing allergic contact dermatitis is primarily based on physical exam and medical history. In some cases
doctors can establish an accurate diagnosis based on the symptoms that the patient experiences and on the
rash's appearance. In the case of a single episode of allergic contact dermatitis, this is all that is necessary.
Chronic and/or intermittent rashes which are not readily explained by history and physical exam often will
benefit from further testing. A patch test (contact delayed hypersensitivity allergy test)
[10]
is a commonly used
examination to determine the exact cause of an allergic contact dermatitis. According to the American
Academy of Allergy, Asthma, and Immunology, "patch testing is the gold standard for contact allergen
identification".
[5]

The patch test consists in applying small quantities of potential allergens to small patches and which are then
placed on the skin.
[11]
After two days, they are removed and if a skin reaction occurred to one of the substances
applied, a raised bump will be noticeable underneath the patch. The tests are again read at 72 or 96 hours after
application.
Patch testing is used for patients who have chronic, recurring contact dermatitis.
[5]
Other tests that may be used
to diagnose contact dermatitis and rule out other potential causes of the symptoms include a skin biopsy and
culture of the skin lesion.
Contact Dermatitis: Facts About Skin Rashes
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You call it a rash. Your doctor calls it dermatitis. Either way, it happens when your skin gets inflamed after it comes in
contact with something.
Contact Dermatitis Causes
Your rash could be caused by an allergy, or by damage to your skin.
If its caused by an allergy, your immune system is involved. After your skin touches something, your immune system
mistakenly thinks its under attack. It springs into action, making antibodies to fight the invader. A chain of events
takes place that causes a release of chemicals like histamine. Thats what causes the allergic reaction -- in this case,
an itchy rash. Its called allergic contact dermatitis.
Usually, you wont get a rash the first time your skin is touching something youre allergic to. But it sensitizes your
skin, and you have an allergic reaction the second time your skin touches it. If you get a rash the first time, chances
are you were exposed to the allergic trigger before and just didnt know it.
Allergic Reaction Triggers
Poison ivy, poison oak, and poison sumac
Hair dyes or straighteners
Nickel, a metal found in jewelry and belt buckles
Leather (chemicals used in tanning leather)
Latex rubber
Citrus fruit, especially the peel
Fragrances in soaps, shampoos, lotions, perfumes, and cosmetics
Some medications that are applied to the skin
When Skin Damage Causes a Rash
Some rashes look like an allergic reaction but really arent because your immune system isnt involved. Instead, you
touched something that directly hurt your skin. The longer that thing stayed on your skin, the worse the reaction. Its
called irritant contact dermatitis.
If you have eczema, youre more likely to get this kind of a rash.
Telling Rashes Apart
Its not easy to tell whether your rash was caused by an allergy or by damage to your skin, because many of the
symptoms can be the same.
With an allergy, symptoms are usually right around where you touched the thing youre allergic to. A rash from skin
damage may be more widespread.
Youll usually see a rash immediately if something is irritating or damaging your skin. With an allergy, it may be a day
or two before the rash shows up.
In both cases, your skin may blister, or you may get a raised red rash.
Your skin will itch and maybe burn. Irritant contact dermatitis (skin damage) tends to be more painful than itchy.
A rash on your hands can be a tell-tale sign of skin damage, because your hands are exposed to so many
substances.
When to See Your Doctor
Call your doctor if your rash isnt better after a couple of days. Usually your doctor can examine you and ask
questions to figure out whats causing the rash.
Depending on how severe your rash is, your doctor may prescribe steroid pills or ointment, and an antihistamine.
Treating a Rash at Home
Dont touch the thing that caused the rash.
If you can wash your skin with mild soap and cool water right after exposure, you may get rid of all or most of the
problem substance. That will help reduce symptoms.
For blisters, try applying cold moist compresses for 30 minutes three times a day.
Oral antihistamines can help relieve itching.
Dont use an antihistamine lotion unless suggested by your doctor, because it sometimes can cause skin irritation or
an allergic reaction.
If the rash covers only a small area, a hydrocortisone cream may be all you need for relief.
Lichen planus
From Wikipedia, the free encyclopedia
Lichen planus
Classification and external resources

Lichen planus affecting the shins.
ICD-10 L43
ICD-9 697.0
DiseasesDB 7452
MedlinePlus 000867
eMedicine derm/233 derm/663
MeSH D008010
Lichen planus is a chronic mucocutaneous disease that affects the skin, tongue, and oral mucosa. The
disease presents itself in the form of papules,
[1]
lesions, or rashes. Lichen planus does not involve lichens, the
fungus/algae symbionts that often grow on tree trunks; the name refers to the dry and undulating, "lichen-like"
appearance of affected skin. It is sometimes associated with oxidative stress,
[2][3]
certain medications and
diseases, however the underlying pathology is currently unknown.
Contents
[hide]
1 Classification
2 Signs and symptoms
3 Cause
4 Treatment
5 References
6 External links
Classification[edit]
Lichen planus may be divided into the following types:
[4]

Configuration
Annular lichen planus
Linear lichen planus
Morphology of lesion
Hypertrophic lichen planus
Atrophic lichen planus
Vesiculobullous lichen planus
Ulcerative lichen planus
Follicular lichen planus
Actinic lichen planus
Lichen planus pigmentosus
Site of involvement
Lichen planus of the palms and soles (Palmoplantar lichen planus)
Mucosal lichen planus
Lichen planus of the nails
Lichen planus of the scalp (leading to cicatricial alopecia)
Inverse lichen planus
Special forms
Drug-induced lichen planus
Lupus erythematosus-lichen planus overlap syndrome
Lichen planus pemphigoides
Keratosis lichenoides chronica
Lichenoid reaction of graft-versus-host disease
Lichenoid keratosis
Lichenoid dermatitis
Signs and symptoms[edit]


Lichen planus affecting the lower lip.


Micrograph of lichen planus. H&E stain.
The typical rash of lichen planus is well-described by the "6 Ps": well-defined pruritic, planar,
purple, polygonal papules and plaques. The commonly affected sites are near the wrist and
the ankle. The rash tends to heal with prominent blue-black or brownish discoloration that
persists for a long time. Besides the typical lesions, many morphological varieties of the rash
may occur. The presence of cutaneous lesions is not constant and may wax and wane over
time. Oral lesions tend to last far longer than cutaneous lichen planus lesions.
Oral lichen planus (OLP) may present in one of three forms.
The reticular form is the most common presentation and manifests as white lacy streaks
on the mucosa (known asWickham's striae) or as smaller papules (small raised area).
The lesions tend to be bilateral and are asymptomatic. The lacy streaks may also be
seen on other parts of the mouth, including the gingiva (gums), the tongue, palate and
lips.The reticular form is the easiest to diagnose. The bullas lesions must be
differentiated from pemphigoid, chemical burns traumatic ulcers. When they break, they
appear as ulcers and need to be differentiated from squamous cell carcinoma.
The bullous form presents as fluid-filled vesicles which project from the surface.The
atrophic and erosive forms must be differentiated from lichenoid drug reactions,SLE,
pemphigoids and other immunobullous disease, candidiasis, erythema multiforme.
The erosive forms (Atrophic LP & Ulcerative LP) present with erythematous (red) areas
that are ulcerated and uncomfortable. The erosion of the thin epithelium may occur in
multiple areas of the mouth (more prominent on the posterior buccal mucosa), or in one
area, such as the gums, where they resemble desquamative gingivitis. Wickham's striae
may also be seen near these ulcerated areas. This form may undergo malignant
transformation, although this is controversial. The malignant transformation rate is
thought to be less than 1%, however it has been reported to be as high as 5%.
[5]
For any
persistent oral lesion of erosive lichen planus that does not respond to topical
corticosteroids, a biopsy is recommended to rule out precancerous (premalignant)
change or malignant transformation.
The microscopic appearance of lichen planus is pathognomonic for the condition
Hyperparakeratosis with thickening of the granular cell layer
Development of a "saw-tooth" appearance of the rete pegs
Degeneration of the basal cell layer with Civatte or colloid body formation. These result
from degenerating epithelial cells.
Infiltration of lymphocytic inflammatory cells into the subepithelial layer of connective
tissue
epithelial connective tissue interphase weakens resulting in formation of histological cleft
known as Max. Joseph's space.
Lichen planus may also affect the genital mucosa vulvovaginal-gingival lichen planus. It
can resemble other skin conditions such as atopic dermatitis and psoriasis.
Rarely, lichen planus shows esophageal involvement, where it can present with erosive
esophagitis and stricturing. It has also been hypothesized that it is a precursor to squamous
cell carcinoma of the esophagus.
[6]

Clinical experience suggests that Lichen planus of the skin alone is easier to treat as
compared to one which is associated with oral and genital lesions.
Cause[edit]
See also: List of human leukocyte antigen alleles associated with cutaneous conditions
Lichen planus is not contagious
[7]
and does not involve any known pathogen. Some lichen
planus-type rashes (known as lichenoid reactions) occur as allergic
reactions to medications for high blood pressure, heart disease and arthritis, in such cases
termed drug-induced lichenoid reactions. These lichenoid reactions are referred to as
lichenoid mucositis (of the mucosa) or dermatitis (of the skin). Lichen planus has been
reported as a complication of chronic hepatitis C virus infection and can be a sign of
chronic graft-versus-host disease of the skin (Lichenoid reaction of graft-versus-host
disease).
[8]
It has been suggested that true lichen planus may respond to stress, where
lesions may present on the mucosa or skin during times of stress in those with the disease.
Lichen planus affects women more than men (at a ratio of 3:2), and occurs most often in
middle-aged adults. The involvement of the mucous membranes is seen frequently and
usually is asymptomatic, but occasionally, LP can be complicated by extensive painful
erosions.
[9]
Lichen planus in children is rare.
Reactions to amalgam fillings may contribute to the oral lesions very similar to lichen planus,
and a systematic review found that many of the lesions resolved after the fillings were
replaced with another material.
[10]

Lichen planus can be part of Grinspan's syndrome.
Treatment[edit]
Care of OLP is within the scope of oral medicine speciality. Currently there is no cure for
lichen planus but there are certain types of medicines used to reduce the effects of the
inflammation. Lichen planus may go into a dormant state after treatment. There are also
reports that lichen planus can flare up years after it is considered cured.
[citation needed]

Medicines used to treat lichen planus include:
Oral and topical steroids.
Oral retinoids
immunosuppressant medications
hydroxychloroquine
tacrolimus
dapsone
Non-drug treatments:
UVB NarrowBand Phototherapy
[11]

Aloe vera
[12]

Purslane
[13]

Aphthous stomatitis
From Wikipedia, the free encyclopedia
Aphthous stomatitis
Classification and external resources

Canker sore on the lower lip
ICD-10 K12.0
ICD-9 528.2
MedlinePlus 000998
eMedicine ent/700 derm/486ped/2672
MeSH D013281
Aphthous stomatitis (also termed canker sores, recurrent aphthous stomatitis, RAS, recurring oral
aphthaeand recurrent aphthous ulceration) is a common cause of benign and non-contagious mouth
ulcers (canker sores). This condition is characterized by the repeated formation of ulcers on the mucous
membrane of the oral cavity (the lining of the mouth), in otherwise healthy individuals.
[1]
These ulcers occur
periodically and heal completely between attacks. Symptoms range from a minor nuisance to interfering with
eating and drinking. The cause is not completely understood, but may involve a T cell mediated immune
response which is triggered by a variety of factors. Different people may have different triggers,
including nutritional deficiencies, local trauma, stress, hormonal influences, allergies, and a genetic
predisposition. The condition is very common, affecting about 20% of the general population. There is no cure,
and treatments are aimed at reducing pain and speeding the healing process. Often, the onset of the condition
is during childhood or adolescence and usually lasts for several years before gradually disappearing, with or
without any form of treatment.
Contents
[hide]
1 Classification
o 1.1 Minor aphthous ulceration
o 1.2 Major aphthous ulceration
o 1.3 Herpetiform ulceration
o 1.4 RAS type ulceration
2 Signs and symptoms
3 Causes
o 3.1 Primary immuno-dysregulation
o 3.2 Decrease of the mucosal barrier
o 3.3 Increase in antigenic exposure
o 3.4 Systemic disease
4 Diagnosis
5 Treatment
6 Prognosis
7 Epidemiology
8 Naming
9 References
10 External links
Classification[edit]


Aphthous ulcers on the labial mucosa (lower lip is retracted). Note erythematous "halo" surrounding ulcer.
Three variants of aphthous stomatitis exist, distinguished by the size, number and location of the lesions, the
healing time of individual ulcers and whether a scar is left after healing.
Minor aphthous ulceration[edit]
This is the most common type of aphthous stomatitis, accounting for about 80% of all cases. This subtype is
termed minor aphthous ulceration (MiAU),
[2]
or minor recurrent aphthous stomatitis (MiRAS). The lesions
themselves may be referred to as minor aphthae or minor aphthous ulcers. These lesions are generally less
than 10 mm in diameter and affect non-keratinized mucosal surfaces (i.e. the labial and buccal
mucosa, lateral borders of the tongue and the floor of the mouth). Usually several ulcers appear at the same
time, but single ulcers are possible. Healing usually takes seven to ten days and leaves no scar. Between
episodes of ulceration, there is usually an ulcer-free period of variable length before the next episode occurs.
[1]

Major aphthous ulceration[edit]
This subtype makes up about 10% of all cases of aphthous stomatitis.
[3]
It is termed major aphthous ulceration
(MaAU) or major recurrent aphthous stomatitis (MaRAS). Major aphthae (major aphthous ulcers) are similar to
minor aphthae, but are more than 10 mm in diameter and the ulceration is deeper.
[1][3]
Because the lesions are
larger, healing takes longer (about twenty to thirty days), and may leave scars. Each episode of ulceration
usually produces a greater number of ulcers, and the time between attacks is less than seen in minor aphthous
stomatitis.
[3]
Major aphthous ulceration usually affects non keratinized mucosal surfaces, but less commonly
keratinized mucosa may also be involved.
Herpetiform ulceration[edit]
Also termed stomatitis herpetiformis,
[4]
herpetiform ulcers,
[1]
or herpes-like ulcerations, this type of aphthous
stomatitis is so named because the lesions resemble a primary infection with herpes simplex (primary herpetic
gingivostomatitis).
[3]
However, herpetiform ulceration is not caused by herpes viruses. As with all types of
aphthous stomatitis, it is not contagious. These ulcers are less than 1 mm in diameter and occur in variably
sized crops up to one hundred at a time. Adjacent ulcers may merge to form larger, continuous areas of
ulceration. Healing occurs within fifteen days. The ulceration may affect keratinized mucosal surfaces in
addition to non keratinized. Herpetiform ulceration is often extremely painful, and the lesions recur more
frequently than minor or major aphthous ulcers. Recurrence may be so frequent that ulceration is virtually
continuous. It generally occurs in a slightly older age group than the other subtypes. Females are affected
slightly more frequently than males.
[2]

RAS type ulceration[edit]
Aphthous stomatitis occurs in individuals with no associated systemic disease.
[1]
Persons with certain systemic
diseases may be prone to oral ulceration, but this is secondary to the underlying medical condition. Examples
include Behet's disease, Reiter's syndrome, recurrent erythema multiforme, celiac disease, Crohn's
disease, ulcerative colitis, anemia and hematinic deficiency (vitamin B12, folic acid and iron). Recurrent oral
ulceration associated with systemic conditions is termed "RAS type ulceration", "RAS like ulceration" or
"aphthous-like ulcers".
[2]
This kind of ulceration is considered to be separate from true aphthous stomatitis.
[1]

Signs and symptoms[edit]
Persons with aphthous stomatitis have no clinically detectable systemic symptoms or signs (i.e. outside the
mouth).
[2]
Generally, symptoms may include prodromalsensations such as burning, itching or stinging, which
may precede the appearance of any lesion by some hours, and pain, which is often out of proportion to the
extent of the ulceration and is worsened by physical contact, especially with certain foods and drinks (e.g.
acidic). Pain is worst in the days immediately following the initial formation of the ulcer, and then recedes as
healing progresses.
[5]
If there are lesions on the tongue, speaking and chewing can be uncomfortable, and
ulcers on the soft palate, oropharynx or esophagus can cause odynophagia (painful swallowing).
[5]
Severe
disease, characterized by virtual constant ulceration (new lesions developing before old ones have healed),
may cause debilitating chronic pain, weight loss and malnutrition.
[5]
Signs are limited to the lesions themselves.
Aphthous ulcers typically begin as erythematous macules (reddened, flat area of mucosa) which develops into
ulcers that are covered with a yellow-grey fibrinous membrane which can be scraped away. An erythematous
"halo" surrounds the ulcer.
[3]
The size, number, location, healing time and periodicity between episodes of ulcer
formation are all dependent upon the subtype of aphthous stomatitis (see classification).
Causes[edit]
The cause is not entirely clear,
[2]
but is thought to be multifactorial.
[1]
It has even been suggested that aphthous
stomatitis is not a single entity but rather a group of conditions with different causes.
[2]
Multiple research studies
have attempted to identify a causative organism, but aphthous stomatitis appears to be non-contagious, non-
infectious and non-sexually transmissible.
[2]
The mucosal destruction is thought to be the result of a T
cell mediated immune response which involves the generation of T cells, interleukins and tumor necrosis factor
alpha.
[1]
When early aphthous ulcers are biopsied, the histologic appearance shows a dense inflammatory
infiltrate, 80% of which is made up of T lymphocytes.
[3]
Persons with aphthous stomatitis have circulating
lymphocytes which react with peptides 91-105 of heat shock protein 65-60.
[2]
Despite this preferred theory of
immuno-dysregulation held by most researchers,
[3]
there is no association between aphthous stomatitis and
otherautoimmune diseases, and the common autoantibodies are not found, meaning that aphthous stomatitis is
not a classical autoimmune disease.
[2]
Aphthous stomatitis also tends to resolve spontaneously with advancing
age rather than worsen.
[2]
Usually, serum immunoglobulin is at normal levels.
[2]
The triggers for the process of
mucosal destruction are multiple. Different subgroups of individuals with aphthous stomatitis appear to have
different causes for the condition.
[3]
This suggests that there are a number of possible triggers, each of which is
capable of producing the disease in different subgroups.
[3]
These sub-groups have been considered to be in
three general groups, namely primary immuno-dysregulation, decrease of the mucosal barrier and increase in
antigenic exposure.
Primary immuno-dysregulation[edit]
At least 40% of people with aphthous stomaitits have a positive family history, suggesting that some people are
genetically predisposed to suffering with oral ulceration.
[1]
HLA-B12, HLA-B51, HLA-Cw7, HLA-A2, HLA-A11,
and HLA-DR2 are examples of human leukocyte antigen types associated (although inconsistently) with
aphthous stomatitis.
[2][3]
Stress has effects on the immune system, (see Effect of stress on the immune system),
which may explain why some cases directly correlate with stress. E.g., ulceration is exacerbated during
examination periods and lessened during periods of vacation.
[2][3]
Aphthous-like ulceration also occurs in
conditions involving systemic immuno-dysregulation, e.g. cyclic neutropenia and human immunodeficiency
virus infection. In cyclic neutropenia, more severe oral ulceration occurs during periods of severe immuno-
dysregulation, and resolution of the underlying neutropenia prevents the cycle of ulceration. The relative
increase in percentage of CD8+ T lymphocytes, caused by a reduction in numbers of CD4+ T lymphocytes may
be implicated in RAS-type ulceration in HIV infection.
[3]

Decrease of the mucosal barrier[edit]
The thickness of the mucosa may be an important factor in aphthous stomatitis. Usually, ulcers form on non
keratinizing mucosal surfaces in the mouth. Factors which decrease the thickness of mucosa increase the
frequency of occurrence, and factors which increase the thickness of the mucosa correlate with decreased
ulceration. The nutritional deficiencies associated with aphthous stomatitis (B12, folate, and iron) all can cause
a decrease in the thickness of the oral mucosa (atrophy). Local trauma is also associated with aphthous
stomatitis, and it is known that trauma can decrease the mucosal barrier. Hormonal factors are capable of
altering the mucosal barrier. In a small subgroup of females with aphthous stomatits, there are fewer
occurrences of aphthae during the luteal phase of the menstrual cycle or with use of the contraceptive
pill.
[2][3]
This phase is associated with a fall in progestogen levels, mucosal proliferation and keratinization. This
subgroup often experiences remission during pregnancy. Aphthous stomatitis is uncommon in people who
smoke.
[1]
Tobacco use is associated with an increase in keratinization of the oral mucosa.
[3]
In extreme forms,
this may be diagnosed as stomatitis nicotina (smoker's keratosis). This increased keratinization may
mechanically reinforce the mucosa and reduce the tendency of ulcers to form after minor trauma, or present a
more substantial barrier to antigens, but this is unclear. Cessation of smoking is known to sometimes precede
the onset of aphthous stomatitis in people previously unaffected, or exacerbate the condition in those who were
already experiencing aphthous ulceration.
[2]
Despite this correlation, starting smoking again does not usually
lessen the condition.
[6]

Increase in antigenic exposure[edit]
Antigenic stimuli have been implicated as a trigger, e.g. L forms of streptococci, herpes simplex virus, varicella-
zoster virus, adenovirus, and cytomegalovirus.
[3]
Some people with aphthous stomatitis may show herpes virus
within the epithelium of the mucosa, but without any productive infection. In some persons, attacks of ulceration
occur at the same time as asymptomatic viral shedding and elevated viral titers.
[3]
In some subgroups, food
allergy may be involved, and some may respond to strict elimination diets based on the results of patch
testing.
[2][3]
Sodium lauryl sulphate, a detergent present in some brands of toothpaste and oral healthcare
products, may produce oral ulceration.
[2]

Systemic disease[edit]
Systemic disorders Associated with aphthous-like ulceration.
[3]

Behcet's syndrome
Celiac disease
Cyclic neutropenia
Nutritional deficiencies
IgA deficiency
Immunocompromise, e.g. HIV
Inflammatory bowel disease
MAGIC syndrome
PFAPA syndrome
Reiter's disease
Sweet's syndrome
Ulcus vulvae acutum
Main article: Oral ulceration
Aphthous-like ulceration may occur in association with several systemic disorders (see table). These ulcers are
clinically and histopathologically identical to the lesions of aphthous stomatitis, but this type of oral ulceration is
not considered to be true aphthous stomatitis by some sources.
[1]
Some of these conditions may cause
ulceration on other mucosal surfaces (conjunctiva, genitals). Resolution of the systemic condition often leads to
a decreased frequency and severity of the oral ulceration.
[3]
The main feature of Behet disease is aphthous-
like ulceration, but is usually more severe than seen in RAS, and typically resembles major or herpetiforme
ulceration or both.
[7]
MAGIC syndrome is a possible variant of Behet disease. PFAPA (periodic aphthae,
pharyngitis and cervical adenitis) is a rare condition that tends to occur in children. The condition appears to
improve after tonsillectomy or immunosuppression, suggesting a immunologic cause.
[7]
In cyclic neutropenia,
there is a reduction in the level of circulating neutrophils in the blood that occurs about every 21 days.
Opportunistic infections commonly occur and aphthous-like ulceration is worst during this time.
[7]

Nutritional deficiencies may occur without any underlying gastrointestinal disease. Iron, folic acid or vitamin B12
deficiencies may be twice as common in people with RAS, but iron and vitamin supplements only infrequently
improve the ulceration.
[7]
The relationship to vitamin B12 deficiency has been the subject of many studies.
Although these studies found that 0-42% of those with recurrent ulcers suffer from vitamin B12 deficiency, an
association with deficiency is rare. Even in the absence of deficiency, vitamin B12 supplementation may be
helpful due to unclear mechanisms.
[8]

Gastrointestinal disorders are sometimes associated with aphthous-like stomatitis, e.g. Crohn's disease,
ulcerative colitis, Celiac disease, but the link is probably related to nutritional deficiencies caused
by malabsorption.
[7]
Less than 5% of people with RAS have Celiac disease. Again, removal of gluten from the
diet does not usually improve the ulceration.
[7]

Diagnosis[edit]
Diagnosis is mostly based on the clinical appearance and the medical history.
[2]
The most important diagnostic
feature is a history of recurrent, self healing ulcers at fairly regular intervals.
[9]
Although there are many causes
of oral ulceration, recurrent oral ulceration has relatively few causes, most commonly aphthous stomatitis, but
rarely Behet's disease, erythema multiforme and ulceration associated with gastrointestinal disease.
[9][6]
A
systemic cause is more likely in adults who suddenly develop recurrent oral ulceration with no prior
history.
[7]
Tissue biopsy is not usually required, unless to rule out other suspected conditions such as
oral squamous cell carcinoma.
[9]
The histopathologic appearance is not pathognomonic (the appearance is non
specific). Early lesions have a central zone of ulceration covered by a fibrinous membrane. In the conenctive
tissue deep to the ulcer there is increased vascularity and a mixed inflammatory infiltrate composed of
lymphocytes, histiocytesand polymorphonuclear leukocytes. The epithelium on the margins of the ulcer
shows spongiosis and there are many mononuclear cells in the basal third. There are also lymphocytes and
histiocytes in the connective tissue surrounding deeper blood vessels near to the ulcer ("perivascular
cuffing").
[3][9]
Special investigations may be indicated to rule out other causes of oral ulceration. These
include blood tests (e.g. to exclude anemia / deficiencies of iron, folate or vitamin B12 or celiac disease). Many
of the systemic diseases cause other symptoms apart from oral ulceration, e.g. genital ulceration in Behet's
syndrome, which is in contrast to aphthous stomatitis where there is isolated oral ulceration. Patch testing may
be indicated if allergies are suspected (e.g. a strong relationship between certain foods and episodes of
ulceration). Several drugs can cause oral ulceration (e.g. nicorandil), and substitution to another drug may
highlight a causal relationship.
[2]

Treatment[edit]
The vast majority of people with aphthous stomatitis have minor symptoms and do not require any specific
therapy (the pain is tolerable with simple dietary modification during an episode of ulceration).
[5]
Many
different topical and systemic treatments have been proposed (see table),
[1][2][10][7]
sometimes showing little or
no evidence of efficacy when formally investigated.
[1]
Some of the results of interventions for RAS may in truth
represent a placebo effect.
[7]
No therapy is curative, with treatment aiming to relieve pain, promote healing and
reduce the frequency of episodes of ulceration.
[1]

Drug type Action Example(s)
Topical covering agents /
barriers
Reduce
pain
Orobase (often combined with triamcinolone)
Topical analgesics / anesthetics /
anti-inflammatory agents
Reduce
pain
Benzydamine hydrochloride mouthwash or spray, Amlexanox paste,
viscous lidocaine.
Topical antiseptics
Hasten
healing
(prevent
secondary
infection)
Doxycycline, tetracycline, minocycline, chlorhexidine gluconate
Topical mild
potency corticosteroids
Reduce
inflammati
on
Hydrocortisone sodium succinate
Topical moderate
potency corticosteroids
Reduce
inflammati
on
Beclomethasone dipropionate aerosol, fluocinonide, clobetasol, betamethasone
sodium phosphate, dexamethasone
Systemic agents
Various,
mostly
modulating
immune
response
Prednisolone, colchicine, pentoxifylline, azathioprine, thalidomide, dapsone,my
cophenolate mofetil, adalimumab
Amlexanox applied topically is highly-studied and effective in healing; less conclusive research suggests that
vitamin B12 supplementation and the avoidance of sodium lauryl sulfate in toothpaste prevent recurrence.
[11]

Occasionally, in females where ulceration is correlated to the menstrual cycle or to an oral contraceptive,
progestogen or a change in oral contraceptive may be beneficial.
[2]
Trauma can be reduced by avoiding rough
or sharp foodstuffs and by brushing teeth with care. If sodium lauryl sulfate is suspected to be the cause,
avoidance of products containing this chemical may be useful. If investigations reveal deficiency states,
correction of the deficiency may result in resolution of the ulceration. Similarly patch testing may indicate that
food allergy is responsible, and the diet modified accordingly.
[2]
Systemic treatment is usually reserved for
severe disease due to the risk of adverse side effects associated with many of these agents. A systematic
review found that no single systemic intervention was found to be effective.
[1]

Prognosis[edit]
By definition, there is no serious underlying medical condition, and importantly the ulcers do not represent oral
cancer and they are not infectious. However, aphthae are capable of causing significant discomfort. There is a
spectrum of severity, with symptoms ranging from a minor nuisance to disabling.
[5]
Due to pain during eating,
weight loss may develop as a result of severe aphthous stomatitis. Usually, the condition lasts for several years
before spontaneously disappearing in later life.
[2]

Epidemiology[edit]
Reported prevalence ranges from 5 to 66%, but is probably about 20% for most populations,
[3]
making it the
most common disease of the oral mucosa.
[9]
Aphthous stomatitis occurs worldwide, but is more common in
developed countries.
[2]
There is a slightly higher prevalence in higher socioeconomic groups. There is no
gender predilection, and the peak age of onset between ten and nineteen years.
[1]
There have been reports of
racial epidemiologic variation, e.g. in the United States of America, aphthous stomatitis may be three times
more common in white skinned people than black skinned people.
[7]

Naming[edit]
The current most widely used medical term is "recurrent aphthous stomatitis" or simply "aphthous stomatitis",
and colloquially, "canker sores".
[5]
An aphtha is a non specific term that refers to an ulcer of the mouth. The
word is derived from the Greek word aphtha meaning "eruption" or "ulcer". The lesions of several other oral
conditions are sometimes described as aphthae, including Bednar's aphthae (infected, traumatic ulcers on the
hard palate in infants),
[12]
oral candidiasis, and foot-and-mouth disease. When used without
qualification, aphthae commonly refers to lesions of recurrent aphthous stomatitis. Since the word aphtha is
often taken to be synonymous with ulcer, it has been suggested that the term "aphthous ulcer" is redundant,
but it remains in common use.
[13]
Stomatitis is also a non specific term meaning inflammation of the mucous
membrane of the mouth, and again may describe many different conditions. Historically, many different terms
have been used to refer to recurrent aphthous stomatitis or its sub-types. Some of these are still in use, and
include Mikulicz' aphthae (named after Jan Mikulicz-Radecki), Sutton's ulcers (named after Richard Lightburn
Sutton), Suttons disease,
[14]
Sutton's syndrome, pariadenitis mucosa necrotica recurrens,
[2]
(recurrent) oral
aphthae, (recurrent) aphthous ulceration and aphthosis.
[3]

Sialolithiasis
From Wikipedia, the free encyclopedia
Sialolithiasis
Classification and external resources

Calculi (salivary gland stones) removed from the sublingual gland
ICD-10 K11.5
ICD-9 527.5
DiseasesDB 29364
MeSH D015494
Sialolithiasis (also termed salivary calculi,
[1]
or salivary stones),
[1]
is a condition where a calcified mass
forms within a salivary gland, usually in the duct of the submandibular gland (also termed "Wharton's duct").
Less commonly the parotid gland or rarely the sublingual gland or a minor salivary gland may develop salivary
stones.
The usual symptoms are pain and swelling of the affected salivary gland, both of which get worse when
salivary flow is stimulated, e.g. with the sight, thought, smell or taste of food, or with hunger or chewing. This is
often termed "mealtime syndrome".
[2]
Inflammation or infection of the gland may develop as a result.
Sialolithiasis may also develop because of the presence of existing chronic infection of the glands, dehydration
(e.g. use of phenothiazines), Sjgren's syndromeand/or increased local levels of calcium, but in many
instances the cause is idiopathic (unknown).
The condition is usually managed by removing the stone, and several different techniques are available.
Rarely, removal of the submandibular gland may become necessary in cases of recurrent stone formation.
Sialolithiasis is common, accounting for about 50% of all disease occurring in the major salivary glands and
causing symptoms in about 0.45% of the general population. Persons aged 30-60 and males are more likely to
develop sialolithiasis.
[2]

Contents
[hide]
1 Classification
2 Signs and symptoms
3 Causes
4 Diagnosis
5 Treatment
6 Epidemiology
7 References
Classification[edit]
The term is derived from the Greek words sialon (saliva) and lithos (stone), and the Latin -iasis meaning
"process" or "morbid condition". A calculus (plural calculi) is a hard, stone-like concretion that forms within an
organ or duct inside the body. They are usually made from mineral salts, and other types of calculi
include tonsiloliths(tonsil stones) and renal calculi (kidney stones). Sialolithiasis refers to the formation of calculi
within a salivary gland. If a calculus forms in the duct that drains the salivafrom a salivary gland into the mouth,
then saliva will be trapped in the gland. This may cause painful swelling and inflammation of the gland.
Inflammation of a salivary gland is termed sialadenitis. Inflammation associated with blockage of the duct is
sometimes termed "obstructive sialadenitis". Because saliva is stimulated to flow more with the thought, site or
smell of food, or with chewing, pain and swelling will often get suddenly worse just before and during a meal
("peri-prandial"), and then slowly decrease after eating, this is termed meal time syndrome. However, calculi
are not the only reasons that a salivary gland may become blocked and give rise to the meal time syndrome.
Obstructive salivary gland disease, or obstructive sialadenitis, may also occur due to fibromucinous plugs,
duct stenosis, foreign bodies, anatomic variations, or malformations of the duct system leading to a mechanical
obstruction associated with stasis of saliva in the duct.
[2]

Salivary stones may be divided according to which gland they form in. About 85% of stones occur in the
submandibular gland,
[3]
and between 5-10% occur in the parotid gland.
[2]
In about 0-5% of cases, the sublingual
gland or a minor salivary gland is affected.
[2]
When minor glands are rarely involved, caliculi are more likely in
the minor glands of the buccal mucosa and the maxillary labial mucosa.
[4]
Submandibular stones are further
classified as anterior or posterior in relation to an imaginary transverse line drawn between the mandibular first
molar teeth. Stones may be radiopaque, i.e. they will show up on conventional radiographs, orradiolucent,
where they not be visible on radiographs (although some of their effects on the gland may still be visible). They
may also symptomatic or asymptomatic, according to whether they cause any problems or not.
Signs and symptoms[edit]
Signs and symptoms are variable and depend largely upon whether the obstruction of the duct is complete or
partial, and how much resultant pressure is created within the gland.
[1]
The development of infection in the
gland also influences the signs and symptoms.
Pain, which is intermittent, and may suddenly get worse before mealtimes, and then slowly get better
(partial obstruction).
[3]

Swelling of the gland, also usually intermittent, often suddenly appearing or increasing before mealtimes,
and then slowly going down (partial obstruction).
[3]

Tenderness of the involved gland.
[3]

Palpable hard lump, if the stone is located near the end of the duct.
[1][3]
If the stone is near the
submandibular duct orifice, the lump may be felt under the tongue.
Lack of saliva coming from the duct (total obstruction).
[3]

Erythema (redness) of the floor of the mouth (infection).
[3]

Pus discharging from the duct (infection).
[3]

Cervical lymphadenitis (infection).
[3]

Rarely, when stones form in the minor salivary glands, there is usually only slight local swelling in the form of a
small nodule and tenderness.
[1]

Causes[edit]


The major salivary glands (paired on each side). 1. Parotid gland, 2. Submandibular gland, 3. Sublingual gland.
There are thought to be a series of stages that lead to the formation of a calculi (lithogenesis). Initially, factors
such as abnormalities in calcium metabolism,
[3]
dehydration,
[2]
reduced salivary flow rate,
[2]
altered acidity (pH)
of saliva caused by oropharyngeal infections,
[2]
and altered solubility of crystalloids,
[2]
leading to precipitation of
mineral salts, are involved. Other sources state that no systemic abnormality of calcium or phosphate
metabolism is responsible.
[1]

The next stage involves the formation of a nidus which is successively layered with organic and inorganic
material, eventually forming a calcified mass.
[2][3]
In about 15-20% of cases the sialolith will not be sufficiently
calcified to appear radiopaque on a radiograph,
[3]
and therefore be difficult to detect.
Other sources suggest a retrograde theory of lithogenesis, where food debris, bacteria or foreign bodies from
the mouth enter the ducts of a salivary gland and are trapped by abnormalities in the sphincter mechanism of
the duct opening (the papilla), which are reported in 90% of cases. Fragments of bacteria from salivary calculi
were reported to beStreptococci species which are part of the normal oral microbiota and are present in dental
plaque.
[2]

Stone formation occurs most commonly in the submandibular gland for several reasons. The concentration of
calcium in saliva produced by the submandibular gland is twice that of the saliva produced by the parotid
gland.
[3]
The sumbandibular gland saliva is also relatively alkaline and mucous. The submandibular duct
(Warton's duct) is long, meaning that saliva secretions must travel further before being discharged into the
mouth.
[3]
The duct possesses two bends, the first at the posterior border of the mylohyoid muscle and the
second near the duct orifice.
[3]
The flow of saliva from the submandibular gland is often against gravity due to
variations in the location of the duct orifice.
[3]
The orifice itself is smaller than that of the parotid.
[3]
These factors
all promote slowing and stasis of saliva in the submandibular duct, making the formation of an obstruction with
subsequent calcification more likely.
Salivary calculi sometimes are associated with other salivary diseases, e.g. sialoliths occur in two thirds of
cases of chronic sialadenitis,
[4]
although obstructive sialadenitis is often a consequence of
sialolithiasis. Gout may also cause salivary stones,
[4]
although in this case they are composed of uric acid
crystals rather than the normal composition of salivary stones.
Diagnosis[edit]


Swelling of the submandibular gland as seen from the outside


The stone seen in the submandicular duct on the persons right side
Diagnosis is usually made by characteristic history and physical examination. Diagnosis can be confirmed by x-
ray (80% of salivary gland calculi are visible on x-ray), or by sialogram or ultrasound.
Treatment[edit]


Salivary gland stone and the hole left behind from the operation
Sialolithiasis
From Wikipedia, the free encyclopedia
Sialolithiasis
Classification and external resources

Calculi (salivary gland stones) removed from the sublingual gland
ICD-10 K11.5
ICD-9 527.5
DiseasesDB 29364
MeSH D015494
Sialolithiasis (also termed salivary calculi,
[1]
or salivary stones),
[1]
is a condition where a calcified mass
forms within a salivary gland, usually in the duct of the submandibular gland (also termed "Wharton's duct").
Less commonly the parotid gland or rarely the sublingual gland or a minor salivary gland may develop salivary
stones.
The usual symptoms are pain and swelling of the affected salivary gland, both of which get worse when
salivary flow is stimulated, e.g. with the sight, thought, smell or taste of food, or with hunger or chewing. This is
often termed "mealtime syndrome".
[2]
Inflammation or infection of the gland may develop as a result.
Sialolithiasis may also develop because of the presence of existing chronic infection of the glands, dehydration
(e.g. use of phenothiazines), Sjgren's syndromeand/or increased local levels of calcium, but in many
instances the cause is idiopathic (unknown).
The condition is usually managed by removing the stone, and several different techniques are available.
Rarely, removal of the submandibular gland may become necessary in cases of recurrent stone formation.
Sialolithiasis is common, accounting for about 50% of all disease occurring in the major salivary glands and
causing symptoms in about 0.45% of the general population. Persons aged 30-60 and males are more likely to
develop sialolithiasis.
[2]

Contents
[hide]
1 Classification
2 Signs and symptoms
3 Causes
4 Diagnosis
5 Treatment
6 Epidemiology
7 References
Classification[edit]
The term is derived from the Greek words sialon (saliva) and lithos (stone), and the Latin -iasis meaning
"process" or "morbid condition". A calculus (plural calculi) is a hard, stone-like concretion that forms within an
organ or duct inside the body. They are usually made from mineral salts, and other types of calculi
include tonsiloliths(tonsil stones) and renal calculi (kidney stones). Sialolithiasis refers to the formation of calculi
within a salivary gland. If a calculus forms in the duct that drains the salivafrom a salivary gland into the mouth,
then saliva will be trapped in the gland. This may cause painful swelling and inflammation of the gland.
Inflammation of a salivary gland is termed sialadenitis. Inflammation associated with blockage of the duct is
sometimes termed "obstructive sialadenitis". Because saliva is stimulated to flow more with the thought, site or
smell of food, or with chewing, pain and swelling will often get suddenly worse just before and during a meal
("peri-prandial"), and then slowly decrease after eating, this is termed meal time syndrome. However, calculi
are not the only reasons that a salivary gland may become blocked and give rise to the meal time syndrome.
Obstructive salivary gland disease, or obstructive sialadenitis, may also occur due to fibromucinous plugs,
duct stenosis, foreign bodies, anatomic variations, or malformations of the duct system leading to a mechanical
obstruction associated with stasis of saliva in the duct.
[2]

Salivary stones may be divided according to which gland they form in. About 85% of stones occur in the
submandibular gland,
[3]
and between 5-10% occur in the parotid gland.
[2]
In about 0-5% of cases, the sublingual
gland or a minor salivary gland is affected.
[2]
When minor glands are rarely involved, caliculi are more likely in
the minor glands of the buccal mucosa and the maxillary labial mucosa.
[4]
Submandibular stones are further
classified as anterior or posterior in relation to an imaginary transverse line drawn between the mandibular first
molar teeth. Stones may be radiopaque, i.e. they will show up on conventional radiographs, orradiolucent,
where they not be visible on radiographs (although some of their effects on the gland may still be visible). They
may also symptomatic or asymptomatic, according to whether they cause any problems or not.
Signs and symptoms[edit]
Signs and symptoms are variable and depend largely upon whether the obstruction of the duct is complete or
partial, and how much resultant pressure is created within the gland.
[1]
The development of infection in the
gland also influences the signs and symptoms.
Pain, which is intermittent, and may suddenly get worse before mealtimes, and then slowly get better
(partial obstruction).
[3]

Swelling of the gland, also usually intermittent, often suddenly appearing or increasing before mealtimes,
and then slowly going down (partial obstruction).
[3]

Tenderness of the involved gland.
[3]

Palpable hard lump, if the stone is located near the end of the duct.
[1][3]
If the stone is near the
submandibular duct orifice, the lump may be felt under the tongue.
Lack of saliva coming from the duct (total obstruction).
[3]

Erythema (redness) of the floor of the mouth (infection).
[3]

Pus discharging from the duct (infection).
[3]

Cervical lymphadenitis (infection).
[3]

Rarely, when stones form in the minor salivary glands, there is usually only slight local swelling in the form of a
small nodule and tenderness.
[1]

Causes[edit]


The major salivary glands (paired on each side). 1. Parotid gland, 2. Submandibular gland, 3. Sublingual gland.
There are thought to be a series of stages that lead to the formation of a calculi (lithogenesis). Initially, factors
such as abnormalities in calcium metabolism,
[3]
dehydration,
[2]
reduced salivary flow rate,
[2]
altered acidity (pH)
of saliva caused by oropharyngeal infections,
[2]
and altered solubility of crystalloids,
[2]
leading to precipitation of
mineral salts, are involved. Other sources state that no systemic abnormality of calcium or phosphate
metabolism is responsible.
[1]

The next stage involves the formation of a nidus which is successively layered with organic and inorganic
material, eventually forming a calcified mass.
[2][3]
In about 15-20% of cases the sialolith will not be sufficiently
calcified to appear radiopaque on a radiograph,
[3]
and therefore be difficult to detect.
Other sources suggest a retrograde theory of lithogenesis, where food debris, bacteria or foreign bodies from
the mouth enter the ducts of a salivary gland and are trapped by abnormalities in the sphincter mechanism of
the duct opening (the papilla), which are reported in 90% of cases. Fragments of bacteria from salivary calculi
were reported to beStreptococci species which are part of the normal oral microbiota and are present in dental
plaque.
[2]

Stone formation occurs most commonly in the submandibular gland for several reasons. The concentration of
calcium in saliva produced by the submandibular gland is twice that of the saliva produced by the parotid
gland.
[3]
The sumbandibular gland saliva is also relatively alkaline and mucous. The submandibular duct
(Warton's duct) is long, meaning that saliva secretions must travel further before being discharged into the
mouth.
[3]
The duct possesses two bends, the first at the posterior border of the mylohyoid muscle and the
second near the duct orifice.
[3]
The flow of saliva from the submandibular gland is often against gravity due to
variations in the location of the duct orifice.
[3]
The orifice itself is smaller than that of the parotid.
[3]
These factors
all promote slowing and stasis of saliva in the submandibular duct, making the formation of an obstruction with
subsequent calcification more likely.
Salivary calculi sometimes are associated with other salivary diseases, e.g. sialoliths occur in two thirds of
cases of chronic sialadenitis,
[4]
although obstructive sialadenitis is often a consequence of
sialolithiasis. Gout may also cause salivary stones,
[4]
although in this case they are composed of uric acid
crystals rather than the normal composition of salivary stones.
Diagnosis[edit]


Swelling of the submandibular gland as seen from the outside


The stone seen in the submandicular duct on the persons right side
Diagnosis is usually made by characteristic history and physical examination. Diagnosis can be confirmed by x-
ray (80% of salivary gland calculi are visible on x-ray), or by sialogram or ultrasound.
Treatment[edit]


Salivary gland stone and the hole left behind from the operation
Some current treatment options are:
For small stones, hydration, moist heat, NSAIDs occasionally, and having the patient take any food or
beverage that is bitter and/or sour. Sucking on citrus fruits, such as a lemon or orange, may
increase salivation and promote spontaneous expulsion of the stone.
Some stones may be massaged out by a specialist.
An ENT or maxillofacial surgeon may canulate the duct to remove the stone (sialotomy).
A surgeon may make a small incision near the stone to remove it.
Sialendoscopy
To prevent infection while the stone is lodged in the duct, sometimes antibiotics are used. In some cases
when stones continually reoccur the offending salivary duct is removed.
Shock wave therapy for disintegration of the salivary stones can also be effectively used.
[5]

Epidemiology[edit]
The prevalence of salivary stones in the general population is about 1.2% according to post mortem studies,
but the prevalence of salivary stones which cause symptoms is about 0.45% in the general
population.
[2]
Sialolithiasis accounts for about 50% of all disease occurring in major salivary glands, and for
about 66% of all obstructive salivary gland diseases. Salivary gland stones are twice as common in males as in
females. The most common age range in which they occur is between 30 and 60, and they are uncommon in
children.
[2]

October 1936, Vol 34, No. 4 >
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Article | October 1936
ETIOLOGY, PATHOLOGY AND TREATMENT OF LEUKOPLAKIA
BUCCALISWITH A REPORT OF THREE HUNDRED SIXTEEN CASES
FRANCIS P. McCARTHY, M.D.
Arch Derm Syphilol. 1936;34(4):612-623. doi:10.1001/archderm.1936.01470160059007.
Text Size: A A A
Article
References
Comments
ABSTRACT
ABSTRACT | REFERENCES
Leukoplakia buccalis, leukokeratosis or smoker's patch is one of the most common lesions that one encounters in an
examination of the oral cavity. A voluminous literature has been written on the subject over many years, and yet
several facts about the condition need to be elucidated. It is interesting to note how the authorities differ regarding
the relation of syphilitic infection to the development of leukoplakia, and a free discussion by various observers leads
invariably to a considerable difference of opinion as to whether syphilis is the most important causal factor.
For the past several years I have classified the cases of this condition in relation to the etiology and studied the
histologic changes in the various stages of development of the lesion.
This study of leukoplakia was carried on primarily at the clinic in oral medicine at Tufts Dental School and was
extended to include a group of