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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.
In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.
Contact sports are also a potential source of infection with herpetic whitlows.
A genital ulcer is located on the genital area, usually caused by a sexually transmitted disease such as genital herpes, syphilis, chancroid, or "Chlamydia trachomatis". Some other signs of having genital ulcers include enlarged lymph nodes in the groin area, or vesicular lesions, which are small, elevated sores or blisters. The syndrome may be further classified into penile ulceration and vulval ulceration for males and females respectively.
Genital ulcers are not strictly a sign of an STD. They can occur in patients with Behcet's syndrome, lupus, and some forms of rheumatoid arthritis (all non-communicable diseases). Genital tuberculosis, often caused by direct genital contact with infected sputum, can also present as genital ulcer.
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 static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript.
Many HSV-infected people experience recurrence within the first year of infection. 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 and are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy.
The causes of reactivation are uncertain, but several potential triggers have been documented. A 2009 study showed the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to other infections is the likely source of the historic terms 'cold sore' and 'fever 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.
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 experience only minor itching or burning for a few days. Some evidence indicates genetics play a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. After several years, some people become perpetually asymptomatic and no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience longer, more frequent, and more severe episodes. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. 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.
A herpetic whitlow is a lesion (whitlow) on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2. HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions. It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion, and in adults aged 20 to 30 following contact with HSV-2-infected genitals. Symptoms of herpetic whitlow include swelling, reddening and tenderness of the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form individually, then merge and become cloudy. Associated pain often seems large relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks. It may reside in axillary sensory ganglia to cause recurrent herpetic lesions on that arm or digits.
Vaginitis an inflammation of the vagina, such as caused by infection, hormone disturbance and irritation/allergy.
Treatment includes fluid intake, good oral hygiene and gentle debridement of the mouth, as well as oral acyclovir. In healthy individuals the lesions heal spontaneously in 7–14 days without scarring.
Testing peoples blood, including those who are pregnant, who do not have symptoms for HSV is not recommended. This is due to concerns of greater harm than benefit such as relationship problems in the setting of a high rate of tests that may be falsely positive.
As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.
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 around 4–5% annually. Suppressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male-to-female transmission than "vice versa". Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.
However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom people will have of their own infections 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.
In October 2011, the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.
All sores involve a breakdown in the walls of the fine membrane of the vaginal wall. The most common of these are abrasions and small ulcers caused by trauma. While these can be inflicted during rape most are actually caused by excessive rubbing from clothing or improper insertion of a sanitary tampon. The typical ulcer or sore caused by syphilis is painless with raised edges. These are often undetected because they occur mostly inside the vagina. The sores of herpes which occur with vesicles are extremely tender and may cause such swelling that passing urine is difficult. In the developing world, a group of parasitic diseases also cause vaginal ulceration, such as leishmaniasis, but these are rarely encountered in the west. All of the aforementioned local vulvovaginal diseases are easily treated. Often, only shame prevents patients from presenting for treatment.
After a first episode of herpes genitalis caused by HSV-2, there will be at least one recurrence in approximately 80% of people, while the recurrence rate for herpes genitalis caused by HSV-1 is approximately 50%. Herpes genitalis caused by HSV-2 recurs on average four to six times per year, while that of HSV-1 infection occurs only about once per year.
People with recurrent genital herpes may be treated with "suppressive therapy", which consists of daily antiviral treatment using acyclovir, valacyclovir or famciclovir. Suppressive therapy may be useful in those who have at least four recurrences per year but the quality of the evidence is poor. People with lower rates of recurrence will probably also have fewer recurrences with suppressive therapy. Suppressive therapy should be discontinued after a maximum of one year to reassess recurrence frequency.
The thickness of the mucosa may be an important factor in aphthous stomatitis. Usually, ulcers form on the thinner, 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) can all 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. Trauma could occur during injections of local anesthetic in the mouth, or otherwise during dental treatments, frictional trauma from a sharp surface in the mouth such as broken tooth, or from tooth brushing.
Hormonal factors are capable of altering the mucosal barrier. In one study, a small group of females with apthous stomatitis had fewer occurrences of aphthous ulcers during the luteal phase of the menstrual cycle or with use of the contraceptive pill. This phase is associated with a fall in progestogen levels, mucosal proliferation and keratinization. This subgroup often experiences remission during pregnancy. However, other studies report no correlation between aphthous stomatitis and menstrual period, pregnancy or menopause.
Aphthous stomatitis is common in people who smoke, and there is also a correlation between habit duration and severity of the condition. Tobacco use is associated with an increase in keratinization of the oral mucosa. In extreme forms, this may manifest as leukoplakia or 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 microbes and antigens, but this is unclear. Nicotine is also known to stimulate production of adrenal steroids and reduce production of TNF-α, interleukin-1 and interleukin-6. Smokeless tobacco products also seem to protect against aphthous stomatitis. 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. Despite this correlation, starting smoking again does not usually lessen the condition.
Gingivostomatitis symptoms in infants may wrongly be dismissed as teething. "Coincidentally, primary tooth eruption begins at about the time that infants are losing maternal antibody protection against the herpes virus. Also, reports on teething difficulties have recorded symptoms which are remarkably consistent with primary oral herpetic infection such as fever, irritability, sleeplessness, and difficulty with eating." "Younger infants with higher residual levels of antibodies would experience milder infections and these would be more likely to go unrecognized or be dismissed as teething difficulty."
Gingivostomatitis must also be differentiated from herpangina, another disease that also commonly causes ulcers in the oral cavity of children, but is caused by the Coxsackie A virus rather than a herpes virus. In herpangina, ulcers are usually isolated to the soft palate and anterior pillar of the mouth. In herpetic gingivostomatitis, lesions can be found in these locations, but they are almost always accompanied by ulcerations on the gums, lips, tongue or buccal mucosa and/or by hyperemia, hypertrophy or hemorrhage of the gums.
Various antigenic triggers have been implicated as a trigger, including L forms of streptococci, herpes simplex virus, varicella-zoster virus, adenovirus, and cytomegalovirus. 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 titres.
In some instances, recurrent mouth ulcers may be a manifestation of an allergic reaction. Possible allergens include certain foods ("e.g.", chocolate, coffee, strawberries, eggs, nuts, tomatoes, cheese, citrus fruits, benzoates, cinnamaldehyde, and highly acidic foods), toothpastes, and mouthwashes. Where dietary allergens are responsible, mouth ulcers usually develop within about 12–24 hours of exposure.
Sodium lauryl sulphate (SLS), a detergent present in some brands of toothpaste and other oral healthcare products, may produce oral ulceration in some individuals. It has been shown that aphthous stomatitis is more common in people using toothpastes containing SLS, and that some reduction in ulceration occurs when a SLS-free toothpaste is used. Some have argued that since SLS is almost ubiquitously used in oral hygiene products, there is unlikely to be a true predisposition for aphthous stomatitis caused by SLS.
Herpes labialis infection occurs when the herpes simplex virus comes into contact with oral mucosal tissue or abraded skin of the mouth. Infection by the type 1 strain of herpes simplex virus (HSV-1) is most common; however, cases of oral infection by the type 2 strain are increasing. Specifically, type 2 has been implicated as causing 10–15% of oral infections.
Cold sores are the result of the virus reactivating in the body. Once HSV-1 has entered the body, it never leaves. The virus moves from the mouth to remain latent in the central nervous system. In approximately one-third of people, the virus can "wake up" or reactivate to cause disease. When reactivation occurs, the virus travels down the nerves to the skin where it may cause blisters (cold sores) around the lips, in the mouth or, in about 10% of cases, on the nose, chin, or cheeks.
Cold sore outbreaks may be influenced by stress, menstruation, sunlight, sunburn, fever, dehydration, or local skin trauma. Surgical procedures such as dental or neural surgery, lip tattooing, or dermabrasion are also common triggers. HSV-1 can in rare cases be transmitted to newborn babies by family members or hospital staff who have cold sores; this can cause a severe disease called neonatal herpes simplex.
The colloquial term for this condition, "cold sore" comes from the fact that herpes labialis is often triggered by fever, for example, as may occur during an upper respiratory tract infection (i.e. a cold).
People can transfer the virus from their cold sores to other areas of the body, such as the eye, skin, or fingers; this is called "autoinoculation". Eye infection, in the form of conjunctivitis or keratitis, can happen when the eyes are rubbed after touching the lesion. Finger infection (herpetic whitlow) can occur when a child with cold sores or primary HSV-1 infection sucks his fingers.
Blood tests for herpes may differentiate between type 1 and type 2. When a person is not experiencing any symptoms, a blood test alone does not reveal the site of infection. Genital herpes infections occurred with almost equal frequency as type 1 or 2 in younger adults when samples were taken from genital lesions. Herpes in the mouth is more likely to be caused by type 1, but (see above) also can be type 2. The only way to know for certain if a positive blood test for herpes is due to infection of the mouth, genitals, or elsewhere, is to sample from lesions. This is not possible if the afflicted individual is asymptomatic.
The likelihood of the infection being spread can be reduced through behaviors such as avoiding touching an active outbreak site, washing hands frequently while the outbreak is occurring, not sharing items that come in contact with the mouth, and not coming into close contact with others (by avoiding kissing, oral sex, or contact sports).
Because the onset of an infection is difficult to predict, lasts a short period of time and heals rapidly, it is difficult to conduct research on cold sores. Though famciclovir improves lesion healing time, it is not effective in preventing lesions; valaciclovir and a mixture of acyclovir and hydrocortisone are similarly useful in treating outbreaks but may also help prevent them.
Acyclovir and valacyclovir by mouth are effective in preventing recurrent herpes labialis if taken prior to the onset of any symptoms or exposure to any triggers. Evidence does not support L-lysine.
There are many oral and maxillofacial pathologies which are not fully understood.
- Burning mouth syndrome (BMS) is a disorder where there is a burning sensation in the mouth that has no identifiable medical or dental cause. The disorder can affect anyone but tends to occur most often in middle aged women. BMS has been hypothesized to be linked to a variety of factors such as the menopause, dry mouth (xerostomia) and allergies. BMS usually lasts for several years before disappearing for unknown reasons. Other features of this disorder include anxiety, depression and social isolation. There is no cure for this disorder and treatment includes use of hydrating agents, pain medications, vitamin supplements or the usage of antidepressants.
- Aphthous stomatitis is a condition where ulcers (canker sores) appear on the inside of the mouth, lips and on tongue. Most small canker sores disappear within 10–14 days. Canker sores are most common in young and middle aged individuals. Sometimes individuals with allergies are more prone to these sores. Besides an awkward sensation, these sores can also cause pain or tingling or a burning sensation. Unlike herpes sores, canker sores are always found inside the mouth and are usually less painful. Good oral hygiene does help but sometime one may have to use a topical corticosteroid.
- Migratory stomatitis is a condition that involves the tongue and other oral mucosa. The common migratory glossitis (geographic tongue) affects the anterior two thirds of the dorsal and lateral tongue mucosa of 1% to 2.5% of the population, with one report of up to 12.7% of the population. The tongue is often fissured, especially. in elderly individuals. In the American population, a lower prevalence was reported among Mexican Americans (compared with Caucasians and African Americans) and cigarette smokers. When other oral mucosa, beside the dorsal and lateral tongue, are involved, the term migratory stomatitis (or ectopic geographic tongue) is preferred. In this condition, lesions infrequently involve also the ventral tongue and buccal or labial mucosa. They are rarely reported on the soft palate and floor of the mouth.
Vulvitis, inflammation of the vulva, can have a variety of etiologies in children and adolescents, including allergic dermatitis, contact dermatitis, lichen sclerosus, and infections with bacteria, fungi, and parasites. Dermatitis in infants is commonly caused by a soiled diaper being left on for an extended period of time. Increasing the frequency of diaper changes and topical application of emollients are sufficient to resolve most cases. Dermatitis of the vulva in older children is usually caused by exposure to an irritant (e.g. scented products that come into contact with the vulva, laundry detergent, soaps, etc.) and is treated with preventing exposure and encouraging sitz baths with baking soda as the vulvar skin heals. Other treatment options for vulvar dermatitis include oral hydroxyzine hydrochloride or topical hydrocortisone.
Lichen sclerosus is another common cause of vulvitis in children, and it often affects an hourglass or figure eight-shaped area of skin around the anus and vulva. Symptoms of a mild case include skin fissures, loss of skin pigment (hypopigmentation), skin atrophy, a parchment-like texture to the skin, dysuria, itching, discomfort, and excoriation. In more severe cases, the vulva may become discolored, developing dark purple bruising (ecchymosis), bleeding, scarring, attenuation of the labia minora, and fissures and bleeding affecting the posterior fourchette. Its cause is unknown, but likely genetic or autoimmune, and it is unconnected to malignancy in children. If the skin changes are not obvious on visual inspection, a biopsy of the skin may be performed to acquire an exact diagnosis. Treatment for vulvar lichen sclerosus may consist of topical hydrocortisone in mild cases, or stronger topical steroids (e.g. clobetasol propionate). Preliminary studies show that 75% of cases do not resolve with puberty.
Organisms responsible for vulvitis in children include pinworms ("Enterobius vermicularis"), "Candida" yeast, and group A hemolytic "Streptococcus". Though pinworms mainly affect the perianal area, they can cause itching and irritation to the vulva as well. Pinworms are treated with albendazole. Vulvar "Candida" infections are uncommon in children, and generally occur in infants after antibiotic therapy, and in children with diabetes or immunodeficiency. "Candida" infections cause a red raised vulvar rash with satellite lesions and clear borders, and are diagnosed by microscopically examining a sample treated with potassium hydroxide for hyphae. They are treated with topical butoconazole, clotrimazole, or miconazole. "Streptococcus" infections are characterized by a dark red discoloration of the vulva and introitus, and cause pain, itching, bleeding, and dysuria. They are treated with antibiotics.
The exact cause of VIN is unknown. Studies are being done to determine the cause of VIN. The following factors have been associated with VIN:
- HPV (Human Papilloma Virus)
- HSV-2 (Herpes simplex Virus - Type 2)
- Smoking
- Immunosuppression
- Chronic vulvar irritation
- Conditions such as Lichen Sclerosus
Many infections can cause oral ulceration (see table). The most common are herpes simplex virus (herpes labialis, primary herpetic gingivostomatitis), varicella zoster (chicken pox, shingles), and coxsackie A virus (hand, foot and mouth disease). Human immunodeficiency virus (HIV) creates immunodeficiencies which allow opportunistic infections or neoplasms to proliferate. Bacterial processes leading to ulceration can be caused by "Mycobacterium tuberculosis" (tuberculosis) and "Treponema pallidum" (syphilis).
Opportunistic activity by combinations of otherwise normal bacterial flora, such as aerobic streptococci, "Neisseria", "Actinomyces", spirochetes, and "Bacteroides" species can prolong the ulcerative process. Fungal causes include "Coccidioides immitis" (valley fever), "Cryptococcus neoformans" (cryptococcosis), and "Blastomyces dermatitidis" ("North American Blastomycosis"). Entamoeba histolytica, a parasitic protozoan, is sometimes known to cause mouth ulcers through formation of cysts.
Many drugs can cause mouth ulcers as a side effect. Common examples are alendronate (a bisphosphonate, commonly prescribed for osteoporosis), cytotoxic drugs (e.g. methotrexate, i.e. chemotherapy), non-steroidal anti-inflammatory drugs, nicorandil (may be prescribed for angina) and propylthiouracil (e.g. used for hyperthyroidism). Some recreational drugs can cause ulceration, e.g. cocaine.
Bacterial
- (Plaque-induced) gingivitis—A common periodontal (gum) disease is Gingivitis. Periodontal refers to the area the infection affects, which include the teeth, gums, and tissues surrounding the teeth. Bacteria cause inflammation of the gums which become red, swollen and can bleed easily. The bacteria along with mucus form a sticky colorless substance called plaque which harbours the bacteria. Plaque that is not removed by brushing and flossing hardens to form tartar that brushing doesn't clean. Smoking is a major risk factor. Treatment of gingivitis is dependent on how severe and how far the disease has progressed. If the disease is not too severe it is possible to treat it with chlorhexidine rinse and brushing with fluoride toothpaste to kill the bacteria and remove the plaque, but once the infection has progressed antibiotics may be needed to kill the bacteria.
- Periodontitis—When gingivitis is not treated it can advance to periodontitis, when the gums pull away from the teeth and form pockets that harbor the bacteria. Bacterial toxins and the body's natural defenses start to break down the bone and connective tissues. The tooth may eventually become loose and have to be removed.
- Scarlet fever is caused by streptococci species, and starts as tonsilitis and pharyngitis before involving the soft palate and the tongue. It usually occurs in children where a fever occurs and a rash develops on the skin. It is treated with penicillin and the prognosis is generally excellent.
Viral
- Herpes simplex (infection with herpes simplex virus, or HSV) is very common in the mouth and lips. This virus can cause blisters and sores around the mouth (herpetic gingivostomatitis) and lips (herpes labialis). HSV infections tend to recur periodically. Although many people get infected with the virus, only 10% actually develop the sores. The sores may last anywhere from 3–10 days and are very infectious. Some people have recurrences either in the same location or at a nearby site. Unless the individual has an impaired immune system, e.g., owing to HIV or cancer-related immune suppression, recurrent infections tend to be mild in nature and may be brought on by stress, sun, menstrual periods, trauma or physical stress.
- Mumps of the salivary glands is a viral infection of the parotid glands. This results in painful swelling at the sides of the mouth in both adults and children. The infection is quite contagious. Today mumps is prevented by getting vaccinated in infancy. There is no specific treatment for mumps except for hydration and painkillers. Sometimes mumps can cause inflammation of the brain, testicular swelling or hearing loss.
Fungal
- Oral candidiasis is by far the most common fungal infection that occurs in the mouth. It usually occurs in immunocompromised individuals. Individuals who have undergone a transplant, HIV, cancer or use corticosteroids commonly develop candida of the mouth and oral cavity. Other risk factors are dentures and tongue piercing. The typical signs are a white patch that may be associated with burning, soreness, irritation or a white cheesy like appearance. Once the diagnosis is made, candida can be treated with a variety of anti fungal drugs.
This is a rare inflammatory condition of the minor salivary glands, usually in the lower lip, which appears swollen and everted. There may also be ulceration, crusting, abscesses, and sinus tracts. It is an acquired disorder, but the cause is uncertain. Suspected causes include sunlight, tobacco, syphilis, poor oral hygiene and genetic factors. The openings of the minor salivary gland ducts become inflamed and dilated, and there may be mucopurulent discharge from the ducts. A previous classification suggested dividing cheilitis into 3 types based on severity, with the later stages involving secondary infection with bacteria, and increased ulceration, suppuration and swelling: Type 1, Simple; Type 2, Superficial suppurative ("Baelz's disease"); and Type 3, Deep suppurative ("cheilitis glandularis epostemetosa"). Cheilitis glandularis usually occurs in middle-aged and elderly males, and it carries a risk of malignant transformation to squamous cell carcinoma (18% to 35%). Preventative treatment such as vermilionectomy ("lip shave") is therefore the treatment of choice.
Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.
Vulvitis is inflammation of the vulva, the external female mammalian genitalia that include the labia majora, labia minora, clitoris, and introitus (the entrance to the vagina). It may co-occur with vaginitis, inflammation of the vagina, and may have infectious or non-infectious causes.
A wide variety of possible causes and treatments for vulvodynia are currently being explored. Moreover, there are probably several causes of vulvodynia, and some may be individual to the patient.
Possible causes include Sjogren's syndrome, the symptoms of which include chronic vaginal dryness. Others include genetic predisposition to inflammation, allergy or other sensitivity (for example: oxalates in the urine), an autoimmune disorder similar to lupus erythematosus or to eczema or to lichen sclerosus, infection (e.g., yeast infections, bacterial vaginosis, HPV, HSV), injury, and neuropathy—including an increased number of nerve endings in the vaginal area. Some cases seem to be negative outcomes of genital surgery, such as a Labioplasty. Initiation of hormonal contraceptives that contain low- dose estrogen before the age of 16 could predispose women to vulvar vestibulitis syndrome. A significantly lower pain threshold, especially in the posterior vestibulum, has also been associated with the use of hormonal contraceptives in women without vulvar vestibulitis syndrome. Pelvic floor dysfunction may be the underlying cause of some women's pain.