Leukoplakia-Definition, Epidemiology, Clinical presentation, Aetiopathogenisis, Diagnosis, Treatment, Prognosis and complication, Prevention

Definition

Leukoplakia is the most common premalignant or "potentially malignant" lesion of the oral mucosa.

Leukoplakia is a predominantly white lesion of the oral mucosa than cannot be clinicopathologically characterized as any other definable lesion.

The term leukoplakia is a clinical descriptor only and should not be used once histological information is available. On the other hand, the terms keratosis and dyskeratosis are histological features and should not be used as clinical terms.

Based on clinical examinations a provisional diagnosis of leukoplakia is made when the lesion cannot be clearly diagnosed as any other disease of the oral mucosa with a white appearance. A definitive diagnosis is made as a result of the identification, and if possible elimination, of suspected etiological factors and, in the case of persistent lesions, histopathological examination confirm the diagnosis.

Epidemiology

The incidence and prevalence of leukoplakia vary in different parts of the world.

In general the reported prevalence ranges from 0.2 to 5%, with remarkable regional differences: India (0.2-4.9%), Sweden (3.6%), Germany (1.6%), Holland (1.4%).

Leukoplakia is seen most frequently in middle-aged and older men.

Gender distribution is also variable. Men are more affected in some countries, while this is not the case in the Western world.

Clinical presentation

Leukoplakia can be either solitary or multiple.

Leukoplakia may appear on any site of the oral cavity, the most common sites being: buccal mucosa, alveolar mucosa, floor of the mouth, tongue, lips and palate.

Classically two clinical types of leukoplakia are recognised: homogeneous and non-homogeneous, which can co-exist.

Homogeneous leukoplakia is defined as a predominantly white lesion of uniform flat and thin appearance that may exhibit shallow cracks and that has a smooth, wrinkled or corrugated surface with a consistent texture throughout. This type is usually asymptomatic.

Non-homogeneous leukoplakia has been defined as a predominant white or white-and-red lesion ("eritroleukoplakia") that may be either irregularly flat, nodular ("speckled leukoplakia) or exophytic ("exophytic or verrucous leukoplakia"). These types of leukoplakia are often associated with mild complaints of localised pain or discomfort.

Proliferative verrucous leukoplakia is an aggressive type of leukoplakia that almost invariably develops into malignancy. This type is characterised by widespread and multifocal appearance, often in patients without known risk factors.

In general, non-homogeneous leukoplakia has a higher malignant transformation risk, but oral carcinoma may develop from any leukoplakia.

Aetiopathogenesis

The aetiology of leukoplakia is still unclear. Although, tobacco seems to be the major inductor factor, its association cannot be determined in all cases.

A variety of smokeless tobacco habits have been reported as leukoplakia inductors: e.g. snuff, chewing. These lesions have shown to have a low malignant transformation risk.

A higher malignant transformation rate has been reported in Candida-infected leukoplakias. However, there is not an agreement of how this lesion should be named "Candida-leukoplakia" or "hyperplastic candidosis", and whether Candida infection is the cause of leukoplakia or is an infection superimposed in a pre-existing lesion.

The possible implication of human papillomavirus (HPV) and others virus has been studied. High risk HPV (16 and 18) have been associated with oral cancer.

Other factors such as alcohol, inadequate diet, vitamin deficiency (e.g. vitamin A and C), areca nut (betel), different mouthwashes, chronic traumatic irritation, poor oral hygiene, poor socio-economic status, galvanism, and even genetic factors have considered and studied in leukoplakia.

Diagnosis

Leukoplakia diagnosis has clinical and histopathological approaches.

- Provisional Clinical Diagnosis: clinical evidence from a single visit, using inspection and palpation as the only diagnostic means.

- Definitive Clinical Diagnosis: clinical evidence obtained by lack of changes after eliminating suspected etiologic factors during a follow-up period of 2-4 weeks (In some cases the time may be longer).

- Histopathologically Proven Diagnosis: definitive clinical diagnosis complemented by biopsy in which, histopathologically, no other definable lesion is observed.

Differential diagnosis includes lichen planus, lupus, leukoedema, candidosis, white sponge naevus, frictional lesions, morsicatio lesions, contact lesions, and smoker’s palate.

Histopathological study of leukoplakia allows the clinician: 1.- to exclude any other definable lesions; and 2.- to establish the degree of epithelial dysplasia, if present.

It may be hazardous to just observe a white lesion without having taken a biopsy. It is important to biopsy the clinically most suspicious areas, especially the non-homogeneous zones or any associated red areas.

Other diagnostic methods such toluidine blue staining or Lugol’s iodine, mycological culture and cytology might be helpful, but they do not replace the biopsy.

Treatment

There are different treatments for leukoplakia, which have shown different results.

However, the risk of malignant transformation is not completely eliminated by any of the current therapies.

Initial treatment of a white oral lesion is the elimination of the possible aetiological factors: e.g. trauma, Candida, tobacco use etc. Complete and definitive cessation of tobacco is obligatory in patients with leukoplakia.

Presence of epithelial dysplasia in persistent lesions is a crucial aspect to consider, although measurement of DNA ploidy may be more reliable.

Complete surgical removal (leaving free-lesion borders) is recommended in cases with epithelial dysplasia. In cases without epithelial dysplasia the decision concerning further treatment or not, is influenced by the extent and location of the lesion as well as the patient ‘s medical condition.

Apart from surgical excision, other treatment modalities available include cryosurgery, laser surgery, retinoids, beta-carotene, bleomycin, calcipotriol, photodynamic therapy, etc.

The major drawbacks for most current agents are the frequency of adverse effects and the recurrence of lesions when treatment is discontinued.

Prognosis and complication

The malignant transformation rate of oral leukoplakia varies from 0 to 33%. Overall, 3 to 8% of leukoplakias develop malignant transformation in a average follow-up period of five years.

Any leukoplakia could transform into a carcinoma, even those which did not show epithelial dysplasia initially (or in which dysplasia happened to be absent from the biopsy taken). The main problem is that the malignant transformation cannot be reliably predicted yet. Nonetheless, some data could help identifying the possible risk. Leukoplakias show a high transformation risk when they: 1.- affect women; 2.- persist for long periods; 3.- appear in non smokers, 4.- are located on the floor of the mouth or tongue; 5.- are seen in patients with a previous head and neck carcinoma; 6.- are non- homogenous; 7.- are infected by Candida; 8.- show epithelial dysplasia, 9.- show DNA aneuploidy. Of all these factors the presence of epithelial dysplasia still seems to be the most important indicator of malignant potential but ploidy may soon be more useful.

Some leukoplakias show an increased recurrence rate (proliferative verrucous leukoplakia; PVL). On the other hand, some leukoplakias disappear spontaneously without any specific therapy.

Regular check-up of these patients is essential, probably every 3, 6 and then 12 months, both in treated and untreated patients.

Prevention

There is no known therapy to prevent development of oral leukoplakia and there is no known therapy to prevent oral squamous cell carcinoma developing from oral leukoplakia;.

It has been demonstrated that a healthy life style and the abstinence of tobacco are the best way to prevent both.

Fresh fruits and vegetables may have a protective effect in the primary prevention of oral cancer and precancer.

Early diagnosis and treatment of leukoplakia, can reduce the high rates of oral cancer morbidity and mortality in many countries.

Screening programs for oral cancer and precancer may be indicated in individuals at risk, such as predetermined age (40-70 years), gender (males in some countries), risk habits (tobacco/alcohol users) and in certain geographic areas with a high incidence of oral cancer.

Leukoplakia of the buccal mucosa

Leukoplakia of the gingiva

Leukoplakia of the lateral tongue

Leukoplakia, histological aspect

Leukoplakia, verrucous variant

TNM staging of head and neck cancer and neck dissection classification

Introduction

The tumor, node, metastasis (TNM) staging system allows clinicians to categorize tumors of the head and neck region in a specific mannerto assist with the assessment of disease status, prognosis, and management. All available clinical information may be used in staging: physical exam, radiographic, intraoperative, and pathologic findings, Other than histopathologic analysis, biomarkers and molecular studies are not yet included in the staging of head and neck cancers. Three categories comprise the system:

T-     the characteristics of the tumor at the primary site 

        (this may be based on size, location, or both);

N-    the degree of regional lymph node involvement; and

M-    the absence or presence of distant metastases.

The specific TNM status of each patient is then tabulated to give a numerical status of Stage I, II, III, or IV. Specific subdivisions may exist for each stage and may be denoted with an a, b, or c status. In general, early-stage disease is denoted as Stage I or II disease, and advanced-stage disease as Stage III or IV disease. Of importance is that any positive metastatic disease to the neck will classify the disease as advanced, except in select nasopharynx and thyroid cancers.

A. Upper aerodigestive tract sites

The majority of tumors arising in the head and neck (other than nonmelanoma skin cancers) arise from the squamous mucosa that lines the upper aerodigestive tract (UADT) and are predominately squamous cell carcinomas. The UADT begins where the skin meets the mucosa at the nasal vestibule and the vermillion borders of the lips and continues to the junction of the cricoid cartilage and the cervical trachea and at the level of the cricoid where the hypopharynx meets the cervical esophagus. The UADT is organized into several major sites that are subdivided to several anatomic subsites. The major sites include (1) the oral cavity, (2) the oropharynx, (3) the hypopharynx, (4) the larynx, (5), the nasopharynx, (6) and the nose and paranasal sinuses.

1. Oral Cavity

The oral cavity is a common site for squamous cell cancers of the UADT, probably because it is the first entry point for many carcinogens. The anterior aspect of the oral cavity is the contact point of the skin with the vermilion of the lips extending posteriorly to the junction of the hard and soft palates, and with the anterior tonsillar pillars and the circumvallate papillae forming the posterior limits. The major subsites of the oral cavity are the lips, anterior tongue, floor of mouth, buccal mucosa, upper and lower alveolar ridges, hard palate, and retromolar trigone. The trigone consists of the mucosa overlying the anterior aspect of the ascending ramus of the mandible. Tumors of the oral cavity tend to spread regionally to lymph nodes of the submandibular region (Level I) and to the upper and middle jugular chain lymph nodes (Levels II and III). Because of accessibility and the risk of involvement of bony structures, treatment with radiotherapy can lead to radionecrosis of the mandible or maxilla. Moreover, oral cavity squamous cell carcinomas may be less sensitive to chemotherapy and radiation, relative to oropharyngeal or laryngeal cancers. Thus, primary treatment for most tumors is surgical. Positive surgical margins, multiple involved lymph nodes, and/or extracapsular tumor extension call for consideration of postoperative chemoradiotherapy, to improve local disease control.

2. Oropharynx

This structure begins where the oral cavity ends at the junction of the hard and soft palates superiorly and the circumvallate papillae inferiorly and extends from the level of the soft palate superiorly, which separates it from the nasopharynx and to the level of the hyoid bone inferiorly, where the hypopharynx begins. The subsites of the oropharynx are the tonsil, base of tongue, soft palate, and pharyngeal walls. Cancers of the oropharynx often metastasize to upper and middle jugular chain lymph nodes (Levels II and III), but can also spread to retropharyngeal lymph nodes, which distinguishes them from oral cavity tumors and must be considered when treating oropharyngeal cancers. Tumors in this site are generally treated with radiotherapy, as a single modality for T 1/2 or N 0/1 stages. Increasingly, some of these cancers are associated with human papilloma virus 16 infection, especially in nonsmokers. However, for patients with more advanced disease, T 3/4 or N 2 b/c/3 staging, chemoradiotherapy most often with a concomitant approach has become standard. Cisplatin, administered during weeks 1, 4, and 7 has most often been studied and may be considered a standard. Nonetheless, other regimens, carboplatin, taxanes, and drug combinations, such as cisplatin or carboplatin with fluorouracil, are also reported. Induction chemotherapy before radiotherapy (or chemoradiotherapy) remains an investigational strategy.

3. Hypopharynx

The hypopharynx has its superior limit at the hyoid bone, where it is contiguous with the oropharynx and it extends inferiorly to the cricopharyngeus muscle, where it meets the cervical esophagus. The major subsites of the hypopharynx are the pyriform sinuses, the postcricoid region, and the pharyngeal walls. Tumors often present here at advanced stages and can be difficult to cure, and because of their location can impact swallowing and speech function adversely. Spread to the upper,middle, and lower jugular lymph nodes (Levels II–IV) and the retropharyngeal nodes is common in these cancers. Two other hallmarks of hypopharyngeal cancers are submucosal spread and skip areas of spread. Surgery had been themainstay of primary treatment for hypopharyngeal cancers formany years, but increasingly radiotherapy and chemoradiotherapy are used to treat cancers in this location with success.

4. Larynx

The larynx is the most complex of the mucosal lined structures of the UADT. Its important roles in speech, swallowing, and airway protection make the treatment considerations of cancers of this structure varied and controversial. The larynx is bordered by the oropharynx superiorly, the trachea inferiorly, and the hypopharynx laterally and posteriorly. The larynx is comprised of a cartilaginous framework, and is subdivided vertically by the vocal cords into the supraglottic, glottic, and subglottic subsites. The supraglottic larynx includes the epiglottis, which has both lingual and laryngeal surfaces, the false vocal cords, the arytenoids cartilages, and the aryepiglottic folds. Anterior to the supraglottis is the pre-epiglottic space. This is a complex space with a rich lymphatic network that contributes to the early and bilateral spread of tumors that arise from supraglottic structures to upper, middle, and lower jugular chain lymph nodes.

The glottic larynx describes the true vocal cords, and where they come together anteriorly at the anterior commissure, as well as where they meet the mobile laryngeal cartilages at the posterior commissure. The glottic larynx extends from the ventricle to 1 cm below the level of the true cords. The vocal cords are lined with stratified squamous epithelia, which contrasts with the pseudostratified ciliated respiratory mucosa lining the remainder of the larynx. Glottic laryngeal cancers tend to metastasize unilaterally and spread regionally less commonly than supraglottic tumors do. Between the thyroid cartilage and the vocal cord lies the paraglottic space, which is continuous with the pre-epiglottic space. This serves as a pathway for submucosal spread of tumors from the glottis to the supraglottis, or vice versa, which is known as transglottic spread. The subglottic larynx starts 1 cm below the vocal folds and continues to the inferior aspect of the cricoid cartilage.While it is rare for tumors to arise initially in the subglottis, tumors arising in the supraglottic or glottis larynx commonly spread in a “transglottic” fashion to involve the subglottic larynx. Subglottic tumors tend to metastasize to paratracheal (Level VI) as well as middle or lower jugular lymph (Levels III and IV) node groups.

Treatment of laryngeal cancers varies widely from center to center, and for early-stage lesions radiotherapy or transoral endoscopic excision are the most common treatment options. Both yield excellent tumor control, but proponents of each modality often disagree on the functional sequelae of the two types of treatment. However, good long-term functional data are lacking. Treatment of more advanced tumors can be even more controversial, but while total laryngectomy was long held as the gold standard for treating T3 and T4 larynx cancers, chemoradiotherapy has been shown to be quite effective in achieving local regional control, survival, and organ preservation. Concomitant chemoradiotherapy may be most appropriate for T3 primary lesions. Treatment of both sides of the neck must be taken into consideration when treating supra- and subglottic tumors, and unilateral neck treatment is considered for patients with advanced glottic tumors.

5. Nasopharynx

The nasopharynx is a cuboidal structure bounded anteriorly by the choanae at the back of the nose where pseudostratified ciliated columnar cells are found. The roof and posterior walls of the nasopharynx are made up of the sphenoid bone and the upper cervical vertebrae, covered with a stratified squamous epithelial lining. Inferiorly, at the level of the soft palate, the nasopharynx meets the superior oropharynx. The opening of the Eustachian tube is found at the posterior-superior aspect of either lateral nasopharyngeal wall; therefore, impingement of this opening by a nasopharyngeal tumor can lead to Eustachian dysfunction manifested by a middle-ear effusion and hearing loss. Thus, all adult patients with an unexplained unilateral middle-ear effusion, particularly in areas where nasopharyngeal carcinoma is endemic (such as southern China, northern Africa, and Greenland), should have their nasopharynx examined. The adenoids, consisting of mucosa-covered lymphoid tissue, are found posteriorly and superiorly in the nasopharynx and are more prominent in children than adults.

While minor salivary tumors can occur in the nasopharynx, most nasopharyngeal cancers are derived from the mucosal lining and fit into one of the three histologic subtypes described by the World Health Organization (WHO). WHO Type I nasopharyngeal carcinoma (NPC) is keratinizing squamous carcinoma, andWHO Type II is nonkeratinizing squamous cell carcinoma.WHO Type III is an undifferentiated tumor, also known as lymphoepithelioma. The Epstein- Barr virus is thought to play a pathogenic role in the development of Type II and III tumors. Nasopharyngeal carcinoma may also metastasize to retropharyngeal and parapharyngeal lymph nodes, as well as lymph nodes along the upper, lower, and middle jugular (Levels II–IV) chains and the posterior triangle of the neck (Level V). Earlystage

NPC is most often treated with radiotherapy alone, and in more advanced cases, T 3/4 N +/ concomitant chemotherapy is being increasingly utilized. Surgery is rarely used in salvage situations at the primary site or neck.

6. Nasal Cavity and Paranasal Sinuses

The paranasal sinuses consist of the paired maxillary sinuses, the superior frontal sinuses, the bilateral ethmoid system, and the central spenoids. This region includes the lining of the nasal cavity (medial maxillary walls) as well as the nasal septum. The majority of sinonasal carcinomas arise in the maxillary sinuses and are most commonly squamous cell carcinomas, although adenocarcinomas are described, especially in woodworkers. Because of inherent bone involvement, initial treatment is usually surgical, with consideration for adjuvant radiation therapy based upon stage and pathologic findings. Reconstruction and rehabilitation, especially in cases with orbital involvement, may be prosthetic or tissue based. Sinonasal carcinomas of the anterior skull base include a variety of pathologies.

Standard treatment is multidisciplinary, including craniofacial surgical intervention with adjuvant radiation and chemotherapy. B. Radiation Therapy and Chemotherapy

External beam radiation therapy (RT) alone or in conjunction with chemotherapy has a well-established role in the treatment of head and neck cancer as definitive therapy or as adjuvant to primary surgical treatment. The last two decades have seen tremendous technological developments in targeting and delivery of RT in a complex treatment site such as the head and neck. Three-dimensional (3-D) conformal RT marked a significant improvement over the conventional two-dimensional 3-field setup in better delineation of tumor volume and nodal volume. This improvement allows limited dosing to normal tissue, while adequately treating the tumor. However, 3-D conformal planning does not always result in optimal shielding ofcritical normal tissues (e.g., salivary glands and visual apparatus), due to current beam constraints.

Intensity-modulated radiation therapy (IMRT) allows for better sparing of such critical normal tissues by modulating the radiation beam in multiple small beamlets, while at the same time adequately covering the tumor volume. With the advent of IMRT, it is also very important for the clinician to be acutely aware of radiologic anatomy (levels of nodal disease, pathways of loco-regional spread of tumor, and delineation of postoperative tumor bed), while utilizing computed tomography, scan magnetic resonance imaging, and positron emission tomography scan for treatment planning. Preoperative clinical and radiologic evaluation of disease is extremely important for postoperative radiotherapy planning, as tissue planes may be obscured after surgery. Such evaluation is also valuable in determining whether ipsilateral or bilateral neck disease needs to be addressed based on tumor location, extent, and size; initial nodal presentation; and likelihood of contralateral nodal involvement.

Certain primary tumor sites have a high risk of retropharyngeal nodal involvement (nasopharynx, piriform sinus, and tongue base), and these nodal groups should be covered in RT target volumes for these tumors. Approximately 20% of anterior tongue and floor of mouth cancers may have skip nodal metastasis to Level IV nodal region, and should be included in RT volumes.

Important considerations in RT planning following surgical resection include a thorough evaluation of the surgical pathology report with respect to resection margins, extension to soft tissue/bone, and perineural or lympho-vascular invasion at the primary site and size; extra-capsular extension (ECE); and the number and level of nodal involvement. Postoperative patients with ECE are at high risk for loco-regional recurrence. Careful adjuvant treatment planning includes consideration of radiation dose (60–66 Gy), addition of concurrent chemotherapy (RTOG 95-01), extension of the RT clinical target volume to include overlying skin, and elective irradiation of contralateral neck nodes. The clinical target volume in radiation therapy of a clinically or pathologically involved neck typically extends up to the skull base to treat the highest neck nodes. In the contralateral elective neck irradiation, the highest treated nodes are jugulodigastric nodes.

Adjuvant RT should ideally begin within 4–6 weeks following primary surgical resection and neck dissection, unless postoperative complications significantly delay wound healing. Delaying adjuvant therapy has been shown to significantly decrease loco-regional control.

American Joint committee on cancer (AJCC)-Tumour staging by site

AJCC tumour staging-Nasopharynx and thyroid

NSAID’s (Non Steroidal Anti Inflammatory Drugs)

Actions of NSAID’s

Anti-inflammatory effects of NSAIDs

This effect of NSAIDs is due to the inhibition of the enzyme COX, which converts arachidonic acid to prostaglandins, TXA2 and prostacyclin.

Acetylsalicylic acid irreversibly inactivates COX-1 and COX-2 by acetylation of a specific serine residue.

Other NSAIDs reversibly inhibit COX-1 and COX-2

Additional anti-inflammatory mechanism may include:

• Interference with the potentiative action of other mediators of inflammation – bradykinin, histamine, serotonin
• Modulation of T-cell function
• Stabilization of lysosomal membranes
• Inhibition of chemotaxis

Analgesic effect of NSAID s

This effect of NSAIDs is thought to be related to the peripheral inhibition of prostaglandin production, but it may also be due to the inhibition of pain stimuli at a subcortical site.

NDAIDs prevent the potentiating action of prostaglandins on endogenous mediators

of peripheral nerve stimulation ( e.g. bradykinin )

Antipyretic effect of NSAIDs

This effect is believed to be related to inhibition of the interleukin-1 and interleukin-6 induced production of prostaglandins in the hypothalmus and the “resetting” of the termoregulatory system, leading to vasodilation and increased heat loss

Clinical uses of NSAIDs

1) Analgesia

2) Inflammation

3) Antipyresis

4) Antiplatelet effect

5) Cancer preventive agents

Adverse effects of NSAIDs

• Gastrointestinal effects: abdominal pain, gastric and duodenal ulcer, diarrhea, pancreatis
• Gastrointestinal hemorrhage, hepatotoxicity
• Renal effect

- Disturbances of renal function with water and sodium retention

• Inhibition of platelet aggregation
• central symptoms: headache, decreased hearing, tinnitus, dizziness, confusion, depression
• Allergic reactions: asthma, rashes, photosensitivity

Pharmacodynamic  interaction NSAIDs with other drugs

• NSAIDs  + hypotensive drugs ( β-blockers, ACE-inhhibitors, diuretics ) = ↓ hypotensive effect
• NSAIDs + ehanol = ↑risk of bleeding from gastrointestinal tract
• NSAIDs  + ticlopidine or clopidogrel = ↑risk of bleeding
• NSAIDs  + lithium = ↑lithium toxicity  
• NSAIDs  + cylosporine or ACE-inhibitors or takrolimus= ↑nephrotoxicity of drugs
• NSAIDs  + fluoroquinolons = ↑ toxic action of fluoroquinolons on CNS
• NSAIDs  +oral antidiabetic drugs  =↑ risk of hypoglycemia
• NSAIDs  + cumarines = ↑risk of bleeding from gastrointestinal tract

Pharmacokinetic interaction NSAIDs with other drugs

• NSAIDs + oral antidiabetic drugs = ↑ risk of hypoglycemia
• NSAIDs  + cumarines =↑risk of bleeding
• NSAIDs  + corticosteroids = ↑risk gastropathy and bleeding from gastrointestinal tract
• NSAIDs  + aminogycosides = ↑ ototoxicity and  nephrotoxicity of aminogycosides
• NSAIDs  + fenytoine or valproinic acid  = ↑action of fenytoine or valproinic acid 
• NSAIDs   + metotrexat or digoxin = ↑action and ↑ toxicity metotrexat or digoxin
• NSAIDs   + tricycles antidepressive drugs  neuroleptics or antiarrhytmic drugs or
• selective serotonin reuptake inhibitors ( SSRI ) = ↑ action of drugs

Classification of NSAIDs According to mechanism of action

1) COX-1 selective inhibitors

    - Acetylsalicylic acid at low dosage

2) Non selective  COX  inhibitors

    - Acetylsalicylic acid at high  dosage

    - Diclofenac

    - Ibuprofen

    - Ketoprofen

    - Flurbiprofen

    - Indomethacin

    - Piroxicam

    - Naproxen

3) More COX-2 selective inhibitors

    -Nimesulid

   - Etodolak

   - Meloxicam

   - Nabumeton

4) COX-2 selective inhibitors

    - Celecoxib

    - Etorcoxib

    - Valdecoxib

Chemical classification of Non-steroidal anti-inflammatory Drugs (NSAIDs)

A: Salicylates

Acetyl salicylic acid (aspirin), sodium salicylate, Mg salicylate, choline salicylate,

Na thio salicylate, salicyl salicylate

B: Propionic acid derivatives

Ibuprofen, ketoprofen, naproxen, oxaprozin, flurbiprofen

C:Indole acetic acid

Indomethacin, sulindac,

D: Substituted anthranilic acids (Rarely used)

Mefenamic acid, meclofenamate Na

E: Pyrrole alkanoic acid (Rarely used)

Tolmetin

F: Oxicams

Piroxicam, meloxicam

G: Difluorophenyl derivatives

Diflunisal

H: Phenyl acetic acid

Diclofenac

I:Acetic acid derivatives

Etodolac

J: Naphthyl acetic acid prodrugs

Nabumetonre

K: Para-amino phenol derivatives

Acetaminophen

Theraputic classification of NSAID s

A: Analgesics

Aspirin, paracetamol

B: Anti-inflammatory

Indomethacin, naproxen, ibuorofen

C: Anti-coagulants

Aspirin

D: Anti-pyretics

Aspirin, paracetamol, indomethacin, celecoxicv, ibuprofen

E: Inflammatory bowel disease

Sulfasalazine, infiximab

F: Anti-cancer drugs

Methotraxate

G: Anti-malarial

Chloroquine, hydroxychloroquine

H: Tissue transplantation

Cyclosporine

I: Chelating agents in wilson’s disease

Penicillamine

J: Anti-gout drugs

Indomethacin, ibuprofen

W.H.O Classification

A: Drugs with weak anti-inflammatory effect

Acetaminophen

B: Drugs with mild to moderate anti-inflammatory effect

Propionic acid derivatives, anthranilic acid derivatives

C: Drugs with marked anti-inflammatory effects

Salicylates, acetic acid derivatives, oxicams, diclofenac, etodolac

Anatomy of the Temporomandibular(TMJ) joint

TMJ is a synovial joint between condyle of the mandible an mandibular fossa on the undersurface of the squamous part of the temporal bone.

The mandible is the single bone with the horizontal horse shoe shaped body, which is continuous at its posterior ends with a pair of vertical rami, each ramus is surmounted by a head or condyle.

The temporomandibular joint allows opening and closing the mouth and complex chewing or side to side movements of the lower jaw.

  

The cranium with which the mandible articulates, is also mechanically, a single componenet, with a mandibular fossa on each side. This complex is in effective functioning joint, as movement cannot take place at one temporomandibular joint, as movement cannot take place at one TMJ without a concomitant movement occurring at the joint on the opposite side.

The temporomandbular joints are thus the bilateral components of a craniomandibular articulation.

The joint is separated into upper and lower joint cavities by a fibrocartilagenous disc within it. Both bone surfaces are covered with a layer of fibrocartilage identical with that of the disc. There is no hyaline cartilage in the joint, so it is an atypical synovial joint.

The capsule is attached high p on the neck of the mandible anteriorly, near the articular margin of the head, but lower down the neck posteriorly. Above, it is attached anteriorly just in front of the articluar eminence of the temporal bone,posteriorly to the squamotympanic fissure,and medially and laterally to the margins of the mandibular fossa. It is lax above the disc, but taut below. The synovial membrane lines the inside of the capsule and the intracapsular posterior aspect of the neck of the mandible.

The articular disc attached around its periphery to the inside of the capsule and to the medial and lateral poles of the head of the mandible. Its upper surface is anteroposteriorly concavoconvex in the sagittal plane to fit the articular eminence and fossa. The inferior surface is concave in adaptation to the condyle. Anteriorly disc is continuous through its capsular attachment with the tendon of lateral pterygoid. 

Posteriorly disc divided into two laminae. The upper fibroelastic lamina is attached to the margin of the mandibular fossa. The lower non elastic fibrous lamina is attached to the neck of the mandible. Between the two laminae is a pad of loosely textured tissue continuing many blood vessels and sensory nerve endings. The disc has two transverse thickened bands it is thinnest and relatively avascular.

Temporal ligament and sphenomandibular ligament reinforce the capsule making it more strong.

Mandibular movements Video

TMJ Disc interferece disorders Videos

The temporomandibular system consists of three basic components; the temporomandibular joint or TMJ, the teeth,and the neuromuscular system.

Temporomandibular disorders come in many forms and varying degrees of severity. Basically TMD is a problem when you either experience pain and/or a loss of jaw function. The pain can range from a mild ache in the morning to a chronic debilitating pain. Loss of function can be mild jaw stiffness to being unable to open the jaw barely at all.

Disc interference disorders are one Category of TMDs.

 

Normal TMJ

 

Anterior disk displacement with reduction

 

Anterior disk displacement without reduction

 

How to Brush Your Teeth Properly

How to Brush your Teeth Properly Video