ORAL PATHOLOGY (NEET MDS/AIIMS) SOME IMPORTANT SYNDROMES

SOME IMPORTANT SYNDROMES

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is a disorder often passed down through families (inherited) in which the person develops intestinal polyps and is at a significantly higher risk for developing certain cancers.


Causes
It is unknown how many people are affected by PJS. However, the National Institutes of Health estimates that it affects about 1 in 25,000 to 300,000 births.
There are two types of PJS:

• Familial PJS is due to a mutation in a gene called STK11. The genetic defect is passed down (inherited) through families as an autosomal dominant trait. That means if one of your parents has this type of PJS, you have a 50:50 chance of inheriting the bad gene and having the disease.
• Sporadic PJS is not passed down through families and appears unrelated to the STK11 gene mutation.

Symptoms

• Brownish or bluish-gray pigmented spots on the lips, gums, inner lining of the mouth, and skin
• Clubbed fingers or toes
• Cramping pain in the belly area
• Dark freckles on and around the lips of a newborn
• Blood in the stool that can be seen with the naked eye (occasionally)
• Vomiting

Exams and Tests
The polyps develop mainly in the small intestine, but also in the colon. A colonoscopy will show colon polyps. The small intestine is evaluated with either a barium x-ray (small bowel series) or a small camera that is swallowed and then take multiple pictures as it travels through the small bowel (capsule endoscopy).
Additional exams may show:

• Intussusception (part of the intestine folded in on itself)
• Noncancerous tumors in the ear (exostoses)

Laboratory tests may include:

• Complete blood count -- may reveal anemia
• Genetic testing
• Stool guaiac
• Total iron-binding capacity (TIBC)

Treatment
Surgery may be needed to remove polyps that cause long-term problems. Iron supplements help counteract blood loss.
Persons with this condition should be monitored by a health care provider and be checked periodically for cancerous polyp changes.


Outlook (Prognosis)
There may be a significant risk of these polyps becoming cancerous. Some studies link PJS and cancers of the gastrointestinal tract, lung, breast, uterus, and ovaries.


Possible Complications

• Intussusception (part of the intestine folds in on itself)
• Polyps that lead to cancer
• Ovarian cysts
• Sex cord tumors

When to Contact a Medical Professional
Call for an appointment with your health care provider if you or your baby have symptoms of this condition. Severe abdominal pain may be a sign of an emergency condition such as intussusception.


Prevention
Genetic counseling is recommended if you are planning to have children and have a family history of this condition.

Stevens Johnson Syndrome
(SJS) is a life-threatening condition affecting the skin in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membranes. Although the majority of cases are idiopathic, the main class of known causes is medications, followed by infections and (rarely) cancers.

Classification
There is agreement in the medical literature that Stevens-Johnson syndrome can be considered a milder form of toxic epidermal necrolysis (TEN). However, there is debate whether it falls on a spectrum of disease that includes erythema multiforme and erythema multiforme major (also known as erythema multiforme majus)
Treatment
All medications should be discontinued, particularly those known to cause SJS reactions. Treatment is initially similar to that of patients with thermal burns, and continued care can only be supportive (e.g. IV fluids) and symptomatic (e.g. analgesic mouth rinse for mouth ulcer); there is no specific drug treatment (2002). Treatment with corticosteroids is controversial since it might aggravate the condition or increase risk of secondary infections. Other agents have been used, including cyclophosphamide and cyclosporine, but none have exhibited much therapeutic success. Intravenous immunoglobulin (IVIG) treatment has shown some promise in reducing the length of the reaction and improving symptoms. Other common supportive measures include the use of topical pain anesthetics and antiseptics, maintaining a warm environment, and intravenous analgesics. An ophthalmologist or optometrist should be consulted immediately, as SJS frequently causes the formation of scar tissue inside the eyelids leading to corneal vascularization and impaired vision, as well as a host of other ocular problems. Also, an extensive physical therapy program ensues after the patient is discharged from the hospital.


Shown in the photographs below is a severe mucositis with epidermal sloughing in a 17 year of female. Symptoms started 24 hours after taking tetracycline for a cough. Blisters first formed with sloughing of the mucosa. The lips, buccal mucosa and soft palate were the main areas of involvement. Stevens Johnson Syndrome (erythema multiforme) is a rare but serious disorder caused by a wide range of drugs and infections: Including antibiotics, non-steroidal anti-inflammatory agents, anticonvulsants and a variety of infections (flue, hepatitis, herpes, typhoid and HIV). Lesion may involve large portions of the skin.

Prognosis is generally good with a 1-5% fatality rate with sloughing involves less than 10% of the skin. However, mortality rate can be greater than 25% when sloughing involves more than 30% of the skin surface. 

Nevoid Basal Cell Carcinoma Syndrome : NBCCS
Basal Cell Nevus Syndrome, Multiple Basal Cell Carcinoma Syndrome, Gorlin syndrome, or Gorlin-Goltz syndrome





It is an inherited group of multiple defects involving the skin,nervous system, eyes, endocrine system, and bones. 

Incidence
About 750,000 new cases of sporadic basal cell carcinoma(BCC) occur each year in the United States. Ultraviolet (UV) radiation from the sun is the main trigger of these cancers, and people with fair skin are especially at risk. Most sporadic BCC arise in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. By comparison, NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal cell carcinomas will occur on non-sun-exposed areas of the body, such as the palms and soles of the feet. These lesions may develop at the base of palmer and plantar pits. One of the prime features of NBCCS is development of multiple BCC at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more manifestations characteristic of it than others

Components

Some or all of the following may be seen in someone with Gorlin Syndrome:
1. Multiple basal cell carcinomas of the skin2. Odontogenic keratocyst: Seen in 75% of patients and is the most common finding. There are usually multiple lesions found in the mandible. They occur at a young age (19 yrs average).3. Rib and vertebrae anomalies4. Intracranial calcification5. Skeletal abnormalities: bifid ribs, kyphoscoliosis, calcification of falx cerebri (diagnosed with AP radiograph)6. Distinct facies: frontal and temporopariental bossing, hypertelorism, and mandibular prognathism 

Diagnostic criteria

Diagnosis of NBCCS is made by having 2 major criteria or 1 major and 2 minor criteria.
The major criteria consist of the following
1. more than 2 BCCs or 1 BCC in a person younger than 20 years;2. odontogenic keratocysts of the jaw3. 3 or more palmar or plantar pits4. calcification of the falx cerebri
5. bifid, fused, or splayed ribs6. first-degree relative with NBCCS.
The minor criteria include the following
1.macrocephaly.2. congenital malformations, such as cleft lip or palate, frontal bossing, or hypertelorism.3. other skeletal abnormalities, such as Sprengel deformity,pectus deformity, or syndactyly.4. radiologic abnormalities, such as bridging of the sella turcica, vertebral anomalies, modeling defects or flame-shaped lucencies of hands and feet.5. ovarian fibroma or medulloblastoma People with NBCCS need education about the syndrome, and may need counseling and support, as coping with the multiple BCCs and multiple surgeries is often difficult. They should reduce UV light exposure, to minimize the risk of BCC. They should also be advised that receiving Radiation therapy for their skin cancers may be contraindicated. They should look for symptoms referable to other potentially involved systems: the CNS, the genitourinary system, the cardiovascular system, and dentition.

Genetic counseling is advised for prospective parents, since one parent with NBCCS causes a 50% chance that their child will also be affected.


Treatment
Treatment is usually supportive.
- Enucleation of the odontogenic cysts can help but new lesions, infections and jaw deformity are usually a result.
- The severity of the basal cell carcinoma determines the prognosis for most patients. Some can be aggressive and cause death.
- Genetic counseling

Gardner's syndrome

Gardner's syndrome is inherited in an autosomal dominant manner. Typically, one parent has Gardner's syndrome. Each of their children, male and female alike, are at 50% risk of inheriting the gene for Gardner's syndrome and manifesting it.


Diagnosis
Gardner's syndrome can be identified based on oral findings, including
multiple impacted

and Supernumerary teeth,
multiple jaw osteomas which give a "cotton-wool" appearance to the jaws,
as well as multiple Odontomas,
congenital hypertrophy of the retinal pigment epithelium (CHRPE),
in addition to multiple Adenomatous polyps of the colon. (Intestinal polyps)

epidermoid cyst

Dermoid tumor (complex-compound)

History

• Many skin findings of Gardner syndrome are evident on full body examination; however, the patient's history of the age at onset and whether lesions are present in family members is important.
• Cysts in Gardner syndrome patients are usually asymptomatic, but they may be pruritic and / or inflamed.
• More than half the patients with Gardner syndrome have dental anomalies. 5Previously Undiagnosed Gardner syndrome may be detected when the patient is evaluated for multiple impacted teeth and Unerupted.

Physical

A full body skin examination for skin tumors and epidermal inclusion cysts is necessary.

• Several factors differentiate cutaneous cysts associated with Gardner syndrome from ordinary cysts.
• Epidermoid cysts of Gardner syndrome occur at an earlier age (around puberty) than ordinary cysts and in less common locations, such as the face, the scalp, and the extremities.
• Gardner syndrome cysts tend to be multiple and are present in the multiple form in 50-65% of patients.
• Similar to ordinary epidermal inclusion cysts, cysts in Gardner syndrome are usually asymptomatic; however, they may be pruritic and/or inflamed, and they may rupture.
• Other skin signs in Gardner syndrome include the following:
• Fibromas
• Lipomas
• Leiomyomas
• Neurofibromas
• Pigmented skin lesions
• Noncutaneous features of Gardner syndrome include the following:
• Desmoid tumors occur as swelling in the anterior abdominal wall and are often preceded by surgical trauma. The incidence of desmoid tumors in FAP is 8.9%.
• Osteomas are required to make the diagnosis of Gardner syndrome. The mandible is the most common location; however, osteomas may occur in the skull and the long bones. Osteomas precede clinical and radiologic evidence of colonic polyposis; therefore, they may be sensitive markers for the disease.
• Colonic adenomatous polyps have a 100% risk of transformation to colonic adenocarcinoma.
• Multifocal pigmented lesions of the fundus are seen in 80% of patients and may present shortly after birth. These lesions can be the first marker of disease.
• Dental abnormalities (eg, unerupted teeth, supernumerary teeth) may occur.
• Other associated neoplasms in Gardner syndrome include the following:
• Periampullary carcinoma (ampulla of Vater; reported in 12% of patients with FAP, usually after colectomy)
• CNS tumors, such as medulloblastoma, glioblastoma, and craniopharyngioma (found in FAP subgroup in Turcot syndrome)
• Thyroid carcinoma (especially in female patients)
• Osteosarcoma
• Chondrosarcoma
• Hepatoblastoma
• Liposarcoma

 Myofascial Pain Syndrome

can occur in patients with a normal temporomandibular joint. It is caused by tension, fatigue, or spasm in the masticatory muscles (medial or internal and lateral or external pterygoids, temporalis, and masseter). Symptoms include bruxism, pain and tenderness in and around the masticatory apparatus or referred to other locations in the head and neck, and, often, abnormalities of jaw mobility. Diagnosis is based on history and physical examination. Conservative treatment, including analgesics, muscle relaxation, habit modification, and bite splinting, usually is effective. 
This syndrome is the most common disorder affecting the temporomandibular region. It is more common among women and has a bimodal age distribution in the early 20s and around menopause. The muscle spasm causing the disorder usually is the result of nocturnal bruxism (clenching or grinding of the teeth). Whether bruxism is caused by irregular tooth contacts, emotional stress, or sleep disorders is controversial. Bruxism usually has a multifactorial etiology. Myofascial pain syndrome is not limited to the muscles of mastication. It can occur anywhere in the body, most commonly involving muscles in the neck and back.

Symptoms and Signs
Symptoms include pain and tenderness of the masticatory muscles and often pain and limitation of jaw excursion. Nocturnal bruxism may lead to headache that is more severe on awakening and that gradually subsides during the day. Such pain should be distinguished from temporal arteritis. Daytime symptoms, including headache, may worsen if bruxism continues throughout the day.
The jaw deviates when the mouth opens but usually not as suddenly or always at the same point of opening as it does with internal joint derangement (see Temporomandibular Disorders: Internal Joint Derangement). Exerting gentle pressure, the examiner can open the patient's mouth another 1 to 3 mm beyond unaided maximum opening.
Diagnosis
Clinical evaluation
A simple test may aid the diagnosis: Tongue blades of 2 or 3 thicknesses are placed between the rear molars on each side, and the patient is asked to bite down gently. The distraction produced in the joint space may ease the symptoms. X-rays usually do not help except to rule out arthritis. If temporal arteritis is suspected, ESR is measured.
Treatment
Mild analgesics
Splint or mouth guard
An anxiolytic at bedtime considered
Physical therapy modalities considered


A plastic splint or mouth guard from the dentist can keep teeth from contacting each other and prevent the damages of bruxism. Comfortable, heat-moldable splints are available from many sporting goods stores or drugstores. Low doses of a benzodiazepine at bedtime are often effective for acute exacerbations and temporary relief of symptoms. Mild analgesics, such as NSAIDs or acetaminophen Some Trade Names
GENAPAP
TYLENOL
VALORIN
, are indicated. Cyclobenzaprine Some Trade Names
FLEXERIL

may help muscle relaxation in some people. Because the condition is chronic, opioids should not be used, except perhaps briefly for acute exacerbations. The patient must learn to stop clenching the jaw and grinding the teeth. Hard-to-chew foods and chewing gum should be avoided. Physical therapy, biofeedback to encourage relaxation, and counseling help some patients. Physical modalities include transcutaneous electric nerve stimulation and “spray and stretch,” in which the jaw is stretched open after the skin over the painful area has been chilled with ice or sprayed with a skin refrigerant, such as ethyl chloride. Botulinum toxin has recently been used successfully to relieve muscle spasm in myofascial pain syndrome. Most patients, even if untreated, stop having significant symptoms within 2 to 3 yr.

Behcet's Syndrome 
Bechet’s syndrome is a rare, chronic, multisystemic inflammatory disease. Although the most commonly encountered mode of manifestations are;
* recurrent oral ulceration,
* genital mucosal ulceration, 
*and eye disease, especially retinal vasculitis, uveitis, and iritis;
* other systems which may be affected include the joints, blood vessels, intestine, the lungs, skin and the central nervous system. 


CAUSE
The cause of this disease is not fully known. It is prevalent in people from around the Mediteranean, the Middle East, China, and Japan; and also thought to have a genetic back-ground. Because many of the findings common to some established immune-complex diseases are also encountered in Bechet’s disease, it is proposed that the cause is most likely an immune reaction triggered by infectious organisms, such as virus or bacteria; or antigens, in genetically predisposed individuals. Although Herpes simplex virus and Streptococcal antigens are suspected, among others, none has been reliably identified.

CLINICAL MANIFESTATIONS
The disease can affect any age. It has been suspected in patients as young as 9 years of age; but most patients are usually in their twenties to thirties. Males are slightly more commonly affected than females. 
The most common lesions in Bechet’s syndrome are recurrent and painful ulcerations of the oral and genital mucosa. The ulcers appear punched out and are surrounded by an inflamed rim. Genital ulcers are particularly painful in the females with the syndrome and may form scars with healing.
Recurrent eye involvement occurs in about 90% of patients. Both eye are eventually involved and may result in blindness.
There may be skin lesions with pustules developing at sites of needle pricks for blood taking. Other skin lesions include papules, vesicles, folliculitis, necrotizing vasculitis, pyoderma, etc.
Neurological manifestations are uncommon, but when present, may present with dementia, impairement of speech, movement and balance; all of which are associated with poor prognosis.
Large joint arthritis are common, but mild, self-limiting and non-deforming.

DIAGNOSIS
There are no established tests, hence diagnosis is made on the basis of clinical examination only. The presence of any three oral, genital, neuro-ocular, and dermatological lesions; or any two plus one other minor criteria, is considered diagnostic. 

MANAGEMENT
The use of colchicine, thalidomide, dapsone and others has yielded controversial results. The use of immunosuppressive medications such as chlorambucil, azathioprine and cyclosporine, prescribed for the most severe cases, and interferon alfa has been reported to be effective. However, they have not been use extensively because of high cost, toxic effects, and the fact that there are no established standard doses or duration of use; and they need to be injected, rather taken orally. 
A new double-blind investigation performed on 40 patients, ages 16 to 52,has shown topical applications of sucralfate suspension to be effective for the treatment of oral ulcerations and genital ulcerations in individuals with Bechet’s syndrome. 
The advantage of the use of sucralfate suspension is its ease of use, inexpensiveness, safety, and effectiveness.

PROGNOSIS
Bechet’s syndrome can be incapacitating, especially when there are eye and neurological involvements. It may follow a variable relapsing and remitting course. There are the risks of blindness, stroke and spinal cord swelling. 
A poor prognosis is associated with the involvement of the central nervous system, bowel perforation and blockage of major blood vessels

Burning mouth syndrome (BMS) is a painful, frustrating condition often described as a scalding sensation in the tongue, lips, palate, or throughout the mouth. Although BMS can affect anyone, it occurs most commonly in middle-aged or older women. 

BMS often occurs with a range of medical and dental conditions, from nutritional deficiencies and menopause to dry mouth and allergies. But their connection is unclear, and the exact cause of burning mouth syndrome cannot always be identified with certainty.

Signs and Symptoms 

Moderate to severe burning in the mouth is the main symptom of BMS and can persist for months or years. For many people, the burning sensation begins in late morning, builds to a peak by evening, and often subsides at night. Some feel constant pain; for others, pain comes and goes. Anxiety and depression are common in people with burning mouth syndrome and may result from their chronic pain. 

Other symptoms of BMS include: 

tingling or numbness on the tip of the tongue or in the mouth

bitter or metallic changes in taste

dry or sore mouth.

Causes 

There are a number of possible causes of burning mouth syndrome, including: 

damage to nerves that control pain and taste

hormonal changes

dry mouth, which can be caused by many medicines and disorders such as Sjögren’s syndrome or diabetes

nutritional deficiencies

oral candidiasis, a fungal infection in the mouth

acid reflux

poorly-fitting dentures or allergies to denture materials

anxiety and depression.

In some people, burning mouth syndrome may have more than one cause. But for many, the exact cause of their symptoms cannot be found. 

Diagnosis 

A review of your medical history, a thorough oral examination, and a general medical examination may help identify the source of your burning mouth. Tests may include: 

blood work to look for infection, nutritional deficiencies, and disorders associated with BMS such as diabetes or thyroid problems

oral swab to check for oral candidiasis

allergy testing for denture materials, certain foods, or other substances that may be causing your symptoms.

Treatment 

Treatment should be tailored to your individual needs. Depending on the cause of your BMS symptoms, possible treatments may include: 

adjusting or replacing irritating dentures

treating existing disorders such as diabetes, Sjögren’s syndrome, or a thyroid problem to improve burning mouth symptoms

recommending supplements for nutritional deficiencies

switching medicine, where possible, if a drug you are taking is causing your burning mouth

prescribing medications to

relieve dry mouth

treat oral candidiasis

help control pain from nerve damage

relieve anxiety and depression.

When no underlying cause can be found, treatment is aimed at the symptoms to try to reduce the pain associated with burning mouth syndrome. 

Helpful Tips 

You can also try these self-care tips to help ease the pain of burning mouth syndrome. 

Sip water frequently.

Suck on ice chips.

Avoid irritating substances like hot, spicy foods; mouthwashes that contain alcohol; and products high in acid, like citrus fruits and juices.

Chew sugarless gum.

Brush your teeth/dentures with baking soda and water.

Avoid alcohol and tobacco products