Simple leukoplakia

Simple leukoplakia refers to dyskeratosis diseases - that is, to those that are accompanied by impaired keratinization. Pathology affects stratified squamous epithelial tissue and can be found in the oral cavity, respiratory tract, urogenital tract, and the anal area. Due to the increased risk of malignant transformation, the disease requires careful diagnosis with histology and cytological analysis of the biomaterial taken. [1] Treatment is mandatory and is prescribed immediately after all diagnostic procedures.

Epidemiology

The incidence of simple leukoplakia is 48% of all cases of this disease. The most common localization is the inner surface of the cheeks, the corners of the mouth, tongue, bladder, cervix, vulva, clitoris. Less commonly, the head of the penis, preputial sac, and anus are affected. Leukoplakia of the oral mucosa is more often diagnosed in India and the southern part of the United States: this is due to the high prevalence of smoking and other use of tobacco.

Malignancy of the pathological process occurs within 12 months to five years from the onset of the disease. Verrucous and erosive-ulcerative leukoplakia are considered more dangerous forms. We have to talk about malignancy in about 2-21% of cases. [2]

The average age of the sick is 30 years. Leukoplakia of the uterine cervix is more often found at the age of 20-30 years. The onset of the development of the disease in childhood or old age is practically not recorded.

Information regarding the epidemiology of simple leukoplakia is contradictory, which is associated with differences in selection criteria (age category, gender and race, the presence of bad habits, eating habits, etc.). There are differences in the diagnosis of the disease: for example, epidemiological data should include the frequency of repeated examinations, the characteristics of the treatment, and also provide for uniform diagnostic criteria.

Men are more likely to become patients with leukoplakia. Idiopathic leukoplakia is diagnosed in 10% of cases.

Causes of the simple leukoplakia

The exact reasons preceding the development of simple leukoplakia are still unknown to scientists. It is assumed that the main role is played by external irritants, such as mechanical, chemical and thermal irritation of the mucous tissue. For example, as gynecological practice shows, every third patient diagnosed with cervical leukoplakia has previously undergone diathermocoagulation procedure. No less often cases of the disease associated with the peculiarities of the profession (work at chemical enterprises, oil and coal mining) are recorded. 

On the oral mucosa, the disease often develops as a result of damage to the mucous membrane by unsuitable prostheses, or by galvanic current, which is formed as a result of the heterogeneity of the prosthetic materials. Smokers often suffer from lip leukoplakia, which is explained by the negative influence of tobacco components and exposure to temperature. [3]

Other reasons may be chronic inflammation and neurodystrophy processes in the mucous tissue. For example, leukoplakia can be the result of stomatitis or gingivitis, vulvovaginitis, cystitis, etc.

The genetic factor cannot be denied, since the disease is often found against the background of congenital dyskeratosis.

Many experts point to a link between the development of leukoplakia and chronic candidiasis .

Risk factors

Additional risk factors for developing simple leukoplakia are:

• hypovitaminosis of vitamins A, E, B ₁₂; [4]
• frequent and deep stress;
• hormonal disorders;
• diseases of the gastrointestinal tract;
• occupational hazard - work at chemical plants, in hot shops;
• endocrine pathologies (diabetes mellitus);
• age-related changes (age over 50);
• HPV.

Pathogenesis

Medicine still cannot give an exact answer to the question of the origin and mechanism of development of simple leukoplakia. Some experts of the last century spoke of the disease as a sign of syphilitic or parasyphilitic lesions. Today, scientists more often point to the viral theory of pathology. In this case, smoking [5] and irritation of mucous tissues (mechanical, chemical, etc.) are considered the most obvious provoking factors . [6]

Another factor is a neurotrophic process in tissues, complicated by a chronic inflammatory reaction. Some experts speak of leukoplakia as a syndrome resulting from prolonged inflammation in the mucous tissue. Such inflammation, in turn, can be triggered by various infectious processes, traumatic, chemical or thermal irritants. [7], [8]

It must be understood that not every site of hyperkeratosis in combination with inflammation should be considered leukoplakia. Many erosive and ulcerative processes are similar to this disease, because they look like foci of localized redness, covered with a light epithelium that can be scraped off. In acute trauma with destruction of mucous tissue, turbidity of the epithelium may be associated with hyperkeratosis, which manifests itself as a reaction to prolonged and regular irritation. Such "fake" leukoplakia disappears immediately after the disappearance of its root cause. [9]

In view of the above, the following forms of leukoplakia are distinguished:

1. A symptom of the type of leukoplakia is not a full-fledged pathology, but only a sign due to an inflammatory reaction in mucous tissues.
2. True leukoplakia is a pathology directly without determining a clear cause.
3. "Fake" leukoplakia is a painful condition that develops as a consequence of other diseases affecting mucous tissue.

In the course of pathological diagnostics, simple leukoplakia reveals itself as a focus of a chronic inflammatory reaction in the mucous tissues, sometimes near the vasculature. Connective tissue fibers in the damaged area have pronounced signs of rarefaction and destruction. The epithelium of the mucous tissue is especially affected: the granular and stratum corneum, which are usually absent, are determined. Acanthosis, devoid of atypical cellular structure, is clearly manifested. During tissue analysis, with a lesion of the bladder, the transformation of the transitional epithelial tissue into stratified squamous epithelium is detected. [10],  [11], [12]

Symptoms of the simple leukoplakia

Simple leukoplakia is most often found on the mucous tissues of the oral cavity (on the inner buccal surface), in the corners of the lips, on the lower lip, less often on the tongue and alveolar processes.  Urogenital leukoplakia is diagnosed in the clitoris, vagina, vulva, uterine neck, head of the penis, urethra, and bladder. Respiratory leukoplakia often affects the vocal cords, epiglottis.

Leukoplakic foci have the appearance of single or numerous light spots with distinct outlines, but with different sizes and shapes. Most often, the first signs go unnoticed, since the pathology does not cause any tangible discomfort. That is why leukoplakia is often detected by chance - for example, when visiting the dentist, during colposcopy, etc. Negative sensations can occur only when the scaphoid fossa of the urethra is damaged (difficulty urinating) and the larynx (coughing, hoarseness, voice change). [13]

The mechanism of development of leukoplakia is phased. Initially, a small area of a non-intense inflammatory process appears on the mucous tissue. Further, the epithelium of the inflamed zone begins to keratinize, a typical light focus is formed, similar to a film plaque, which cannot be removed with a spatula.

Simple leukoplakia can exist for years or transform into verrucous leukoplakia: the affected area becomes denser and becomes convex. Along with areas of keratinization, cracks and ulcers may appear, which is typical for the erosive course of the disease. [14]

Stages

The term "leukoplakia" is considered purely clinical, and is practically not used for morphological description. In pathology, one of four types of changes is usually identified:

• focal epithelial hyperplasia;
• squamous intraepithelial neoplasia 1 tbsp.; (PIN)
• PIN 2 tbsp;
• PIN 3 tbsp.

As a rule, the clinical disease begins with a pre-leukoplakic stage, characterized by an inflammatory process in the mucous membrane. Further, keratinization is observed with the development of flat, or simple leukoplakia.

Forms

Usually, experts divide leukoplakia into several types:

• Actually focal simple leukoplakia, or flat, is expressed by a sharply limited opacity of the mucous membrane. Sometimes such a focus looks like a superficial dense film with a dryish and rough surface. Its color shade ranges from grayish to almost white, depending on the degree of keratinization. Outlines are dentate. In the oral cavity, leukoplakia can have the appearance of a wrinkled film or light folds.
• Verrucous leukoplakia has the appearance of a convex white smooth growth, but sometimes it manifests itself as dense tubercles, convex by about 2.5 mm. Verrucous and simple leukoplakia are often found against the background of each other.
• Erosive leukoplakia is characterized by the appearance of erosive lesions, cracks in the area of a simple or verrucous leukoplakic focus.
• Nicotine leukoplakia is found in people who smoke. It looks like a keratinized hard palate of a light shade, against the background of which reddish blotches are visible (exit ducts of the salivary glands).

There is another classification of the disease, depending on the localization of the disease process:

• Simple leukoplakia of the cervix often proceeds without certain symptoms, and zones of keratinization of the mucous membrane are discovered by chance during a gynecological examination. Some patients may complain about the presence of leucorrhoea with an unpleasant odor and color, itching of the genitals. Sometimes there is an increase in pain during menstrual bleeding, pain during sexual intercourse. Cervical leukoplakia and pregnancy
• Simple leukoplakia of the vulva is a dystrophic transformation of the cellular structures of the vulva, which is accompanied by keratinization processes. This problem is found most often in women who have crossed the threshold of menopause or menopause.
• Simple leukoplakia of the oral cavity often occurs in areas prone to frequent damage to the mucous membrane - for example, with close adhesion or uneven position of the teeth, in the presence of improperly installed fillings or prostheses.

What does a term like "simple leukoplakia without atypia" mean?

Leukoplakia without cell atypia refers to the processes of hyperkeratosis and parakeratosis. When examining smears-prints, keratin lumps, accumulations of surface cellular structures (devoid of a nucleus) are found. The cytoplasm of cells is stained by Papanicolaou in yellow or orange. There may be layers of polygonal keratinizing cells - dyskeratocytes. [15]

A diagnosis of simple leukoplakia without atypia means that there is practically no risk of transformation of the disease into a malignant form.

Complications and consequences

The most undesirable complication of simple leukoplakia can be considered a malignant transformation of the disease - that is, its transformation into a cancerous process. However, verrucous and erosive leukoplakia is most often malignant.

If the painful process affects the cervix, then there is a risk of infertility.

With improper or untimely treatment of laryngeal lesions, some irreversible tissue changes may develop, against which the patient may develop frequent diseases of the ENT organs.

With damage to the bladder, there is a likelihood of the appearance of various chronic disorders of the urinary process. They, in turn, negatively affect the patient's quality of life. [16]

Diagnostics of the simple leukoplakia

In the overwhelming majority of cases, simple leukoplakia is diagnosed without any particular problems when it comes to areas available for examination by a doctor (for example, if the lesions are located in the oral cavity, on the external genitals). To clarify the diagnosis, cytology with histological examination is mandatory.

Cytology helps detect abnormal cells that are characteristic of a precancerous condition. In the process of cytological diagnostics, a lot of multilayer epithelial cells with signs of keratinization are identified. It is important to take into account that the smear cannot cover the underlying layers of tissue, in which signs of atypia may be present. Therefore, for an accurate diagnosis, it is better to take not a smear, but a biopsy.

Histological examination reveals keratinization of the epithelium without the upper functional layer, since the upper epithelial layer is at the parakeratosis or hyperkeratosis stage. Possible hyperactivity and atypicality of the basal cells, which indicates an increased likelihood of malignancy. [17]

Leukoplakia of the uterine cervix is determined during a gynecological examination or colposcopy.

Ancillary analyzes are carried out:

• smear for the presence of antibodies to sexually transmitted diseases;
• bacterial analysis;
• KLA and blood for STDs, HPV, HIV;
• immunogram;
• study of hormonal status.

Instrumental diagnosis is appropriate if laryngeal leukoplakia is suspected: laryngoscopy is performed in conjunction with a biopsy. With urinary leukoplakia or with a lesion of the urethra, it is appropriate to carry out urethroscopy, cystoscopy with mandatory simultaneous biopsy.

Differential diagnosis

Differential diagnosis is carried out with thrush of the oral cavity and genitals, with secondary syphilis , with Bowen's and Keir's diseases, with keratinizing squamous cell carcinoma of , lichen planus . [18]

Cervical leukoplakia and cancer are easily identified using the Schiller test. The affected area in the neck area is treated with Lugol's solution: if atypical cells are present, they will not change their shade. Additionally, a biopsy and a histology of the material removed from the cervix and cervical canal are taken.

Treatment of the simple leukoplakia

Simple leukoplakia, regardless of the location of the painful focus, requires the appointment of complex therapy. Treatment should be aimed at neutralizing the causes that caused the appearance of the problem, as well as correcting the accompanying problems. Treatment measures include:

• elimination of damaging factors that injure the mucous membrane;
• getting rid of bad habits;
• fight against hypovitaminosis;
• treatment of existing diseases of the digestive, endocrine, genitourinary system, somatic diseases, infectious and inflammatory pathologies.

Radical procedures for simple leukoplakia are rarely used. Such measures are relevant only when atypical cells are detected. Usually the patient is carefully examined, the pathological process is monitored. Drug treatment may include taking antibiotics, anti-inflammatory, antiviral, hormonal and immunomodulatory agents. [19]

Medicines that a doctor may prescribe

Hyposensitizing drugs	They are prescribed to suppress the pathogenetic mechanism of the development of the allergic process. Example: Astemizole is taken 10 mg once a day. Possible side effects: paresthesia, myalgia, sleep disturbances.
Keratoplastic funds	They are prescribed to normalize metabolic processes in the epithelium of the mucous tissue. Example: Carotolin is an oil extract from the pulp of rosehip berries, used for applications on the affected mucous tissues of the oral cavity. Possible side effects: allergy.
Immunomodulators	They are prescribed to improve the body's immune response. Example: Immunal is taken 1 tablet 4 times a day for 10 days. Possible side effects: allergic reactions, dizziness, arterial hypotension.
Antiseptic	They are used to accelerate tissue healing. Example: Tantum Verde is used to irrigate the affected areas of the oral cavity 4 times a day. Possible side effects: dry mouth, allergies.
Vitamin remedies	To normalize metabolism in the epithelial tissue, a long course (about 2 months) of vitamin A is prescribed, 10 drops 3 times a day, or Aevit 1 capsule three times a day after meals. This treatment is repeated 2-3 times a year. It is recommended to apply an oil solution of vitamin A to the oral mucosa three times a day for 20 minutes.

Vitamins

For the treatment and prevention of leukoplakia, the prescription of a long course of vitamin A is practiced. There is evidence of the positive use of a combination of retinol acetate with thiamine.  In general, experts recommend prescribing the following vitamin preparations to patients:

• coenzyme Q10 - a source of cellular energy, eliminates vulnerability and accelerates the healing of mucous tissue;
• vitamins B ₃  and B ₆  - normalize the sensitivity of the mucous membranes;
• vitamin A - increases tissue resistance to infectious and inflammatory processes, takes part in metabolic processes.

In case of leukoplakia of the oral cavity, it is especially recommended to use green tea extract, which helps to strengthen the gums, has bactericidal activity and antioxidant properties.

Physiotherapy treatment

Physiotherapy methods for leukoplakia are not decisive, but they can be used at some stages of recovery:

• photodynamic treatment;
• immunostimulation;
• X-ray therapy;
• ozone therapy;
• hydrotherapy (irrigation, baths, showers);
• mud therapy;
• UFO of the lumbosacral zone;
• acupuncture;
• ultrasound.

The essence of photodynamic therapy is the use of light-sensitive components. We are talking about photosensitizers: they are injected into the patient's body, after which they are activated using laser radiation. This method is successfully used to treat many malignant processes, dermatological diseases, to eliminate foci of inflammation. The procedure involves the application of sensitizers, which selectively accumulate in the affected tissue areas. Next, irradiation is carried out with a low-intensity laser with a power of 1-2 W. With this power, it is possible to control the temperature threshold of sensitivity.

The use of ozone-oxygen mixtures during ozone therapy procedures allows to optimize the intracellular microcirculation of vitamins and minerals. In addition, ozone is a good disinfectant and has an effect on oxygen release in tissues, stimulating all biological processes.

Alternative treatment

The vast majority of medical professionals advise against treating leukoplakia with alternative remedies. There are many known cases when such treatment led to the transformation of the disease into a malignant form. However, some patients ignore the warnings and practice alternative methods. In their opinion, the available means make it possible to keep the pathology under control and eliminate painful signs.

Alternative treatment is based on the use of a variety of remedies available in normal household settings. It can be food, plants, etc. For example, 4-6% natural apple cider vinegar is often used to treat painful lesions, which has anti-inflammatory, disinfectant, antifungal, healing and emollient properties. But: in no case should undiluted vinegar or concentrate be used, as it will lead to burn damage to the mucous tissues. For the same reason, leukoplakia foci are not treated with alcohol solutions, green paint, iodine, etc.

It is advised to add pumpkin to the diet of patients suffering from leukoplakia. Pumpkin juice and pulp contains many nutrients necessary for the body, helps cleanse tissues and remove toxic components.

It is also useful to drink a glass of fresh juice of carrots and celery in the morning. To enhance the effect and in the absence of contraindications, a pinch of baking soda is added to the juice. [20]

Herbal treatment

According to alternative healers, the most pronounced effects on leukoplakia are:

• rinsing with saffron water infusion;
• chewing propolis;
• washing with meadowsweet infusion.

Calendula, basil, birch buds, viburnum fruits, motherwort, bay leaf, eucalyptus, dandelion rhizome have a similar positive effect. Plants considered poisonous are not recommended for the treatment of leukoplakia. Such undesirable herbal remedies are celandine, potato color, wormwood, hemlock, etc.

For washing the mucous membrane, an infusion of St. John's wort (1 tbsp. L. Plants per 500 ml of water), sage (1 tsp. Per 200 ml of water), as well as fresh cabbage juice are successfully used.

Homeopathy

Homeopathic treatment for leukoplakia of different localization is carried out against the background of traditional therapy, since it effectively complements each other. A specialist in the field of homeopathy will be able to suggest the most suitable drug, withstand the correct proportions and frequency of use. As a rule, there are no side effects from such treatment: it is easily perceived by patients of any age.

With leukoplakia, homeopathic suppositories have proven themselves well:

• Calendula;
• Propolis;
• Chaga;
• Thuja;
• Femikan.
• Ointment preparations are no less effective:
• Calendula;
• Propolis;
• Arnica;
• Thuja;
• Witch hazel.

Homeopathic remedies often help prevent complications of leukoplakia - for example, sluggish wounds, cracks, ulcers and erosions. However, the use of only homeopathy, without the main traditional treatment, is not encouraged by specialists.

Surgery

The use of surgical treatment in most cases allows you to neutralize all painful foci of leukoplakia and completely get rid of them. The most commonly used technologies are:

• The radio wave method involves removing the affected areas of mucous tissue using a radio wave knife. This method is effective, painless and bloodless, does not require the use of anesthesia, completely excludes postoperative bleeding and infectious complications.
• The cryodestruction method consists in treating the affected tissues with liquid nitrogen, which causes their death. The procedure is painless, lasts no more than fifteen minutes, and the degree of effectiveness (no relapse) is estimated at more than 95%. The only drawback is that after healing, a rough scar may form at the site of the leukoplakia focus.
• The method of chemical coagulation is the treatment of foci with a special chemical composition, which is considered quite effective and practically painless.
• The method of argon plasma coagulation involves cauterization of pathologically altered tissues using radio waves of different power. The method is painless, bloodless, does not leave behind gross cicatricial changes. Moxibustion leaves almost no chance for the development of a microbial infection.

Some situations require surgical excision of the affected area. After such an intervention, as a rule, reconstructive plastic is performed.

If the site of leukoplakia is localized on the laryngeal mucosa, then a microlaryngological operation is prescribed. The urinary mucosa is coagulated during cystoscopy. [21]

Should you remove simple leukoplakia?

Simple leukoplakia, of course, cannot remain without treatment, which must include the eradication of the factors that led to the development of the disease. It is important to get rid of mechanical damaging agents (for example, dentures or dental crowns), quit smoking and drinking alcohol, improve the supply of necessary vitamins to the body, cure existing pathologies of the digestive and endocrine systems, as well as all somatic disorders, infectious and inflammatory processes.

If, with simple leukoplakia, there are no signs of atypia of cellular structures, then the doctor may not insist on carrying out radical treatment in the form of removing problem areas. However, such patients should be monitored with periodic examination. If in the process of diagnostics basal cell hyperactivity and cell atypia are determined, then we should talk about the mandatory removal of the leukoplakia site - and as early as possible. [22]

Removal of the affected mucous tissue is carried out using laser technology or radio waves, diathermocoagulation or electroexction method. For individual patients, surgical surgical excision of the entire affected area (urethra, vagina, etc.) may be recommended, which requires further reconstructive plasty of the organ.

If signs of malignancy of simple leukoplakia are detected, a radical intervention is prescribed with further X-ray therapy.

If simple leukoplakia is found in the larynx region, then microlaryngosurgical surgery may be recommended. For bladder involvement, coagulation is performed by means of cystoscopy. If the disease is characterized by a pronounced increase in symptoms and the spread of the painful process, then organ resection may be required.

Competent and timely therapy, even with a stormy course of pathology, leads to a positive result. Unfortunately, there is no guarantee that the patient will be able to avoid relapses. This is especially true in cases where radical removal was not involved. Therefore, medical supervision is mandatory for the patient's health. It is necessary to be extremely careful about thermotherapy and all kinds of methods of alternative therapy. Such dubious methods of treatment can lead to malignancy and aggravation of the course of the pathology. [23]

Prevention

To prevent the development of simple leukoplakia, it is necessary to eliminate all possible causes and factors for the development of the disease. For example, it is necessary to limit the likelihood of infection entering the body as much as possible, namely:

• strengthen immunity;
• avoid contact with infected people;
• observe sanitary and hygienic rules.

It is imperative to devote time to recreational activities, lead an active lifestyle, eat well and give up all bad habits.

Prevention of the development of oral leukoplakia includes:

• regular sanitation of the oral cavity (getting rid of tartar, correct selection of dentures, timely treatment and restoration of teeth and gums, etc.);
• avoiding the use of too hot, spicy foods, alcohol, as well as medicines without a doctor's prescription;
• to give up smoking;
• exclusion of occupational hazards that adversely affect the mucous membrane;
• exclusion of taking medications not prescribed by a doctor;
• regular preventive visits to doctors (dentist, gynecologist, therapist).

It is important to prevent and promptly detect any mechanical and chemical damage to the mucous membrane, avoid occupational hazards, smoking and alcohol consumption, and prevent hypovitaminosis of vitamins A and B ₂. Preventive measures include early detection and timely treatment of any disease.

Patients are recommended to undergo periodic prophylactic examinations with further registration in the dispensary if chronic pathologies of mucous tissues are detected.

Many patients feel that they are quite competent in terms of sanitation and personal hygiene, and they do not need special explanations about this. But practice shows that intelligible explanations and demonstrations of sanitary and hygienic rules and norms cannot be "superfluous": it is important to instill the correct hygiene skills and even monitor the success of their implementation. It is noticed that all the doctor's efforts to cure simple leukoplakia can be in vain if the patient ignores advice on personal hygiene - in particular, of the genitals and oral cavity.

Maintaining an adequate hygienic status in the body will ensure the normal course of many physiological processes. For this reason, explanations regarding the rules and methods of self-organization and a healthy lifestyle are an important goal of all representatives of the medical profession.

Forecast

With early detection of simple leukoplakia, complete healing is achieved in 99 out of a hundred patients. Thus, the prognosis can be considered quite favorable, subject to early detection of the disease. However, if the provoking factors are not eradicated, each patient remains at risk of re-developing the pathology. And in some cases, a simple painful process acquires a malignant course - for example, this happens in 15% of patients with diagnosed cervical leukoplakia.

After the course of treatment, all patients who have undergone leukoplakia should be registered with a dispensary. Women should visit the gynecological office twice a year for a cytological smear. Colposcopy and analysis for human papillomavirus are mandatory. If within two years the development of the disease has not resumed, then the patient is removed from the register.

Simple leukoplakia, in contrast to the verrucous and erosive-ulcerative forms, is not so often transformed into a malignant disease. However, such a development of events cannot be ruled out. Pathology is subject to compulsory treatment - first of all, to prevent the development of complications and to inhibit the painful process. The appearance of complications significantly impairs the quality of the prognosis.