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« on: September 19, 2006, 08:55:40 am »

Sjögren's Syndrome
 
 
 
Sjögren's syndrome is characterized by excessive dryness of the eyes, mouth, and other mucous membranes.

Sjögren's syndrome is thought to be an autoimmune disorder, but its cause is not known. It is more common in women than in men.

White blood cells infiltrate the glands that secrete fluids, such as the salivary glands in the mouth and the tear glands in the eyes. The white blood cells injure the glands, resulting in a dry mouth and dry eyes—the hallmark symptoms of this syndrome.

Symptoms

In some people, only the mouth or eyes are dry (a condition called sicca complex or sicca syndrome). Dryness of the eyes may severely damage the cornea, resulting in a scratchy or irritated sensation, and a lack of tears can cause permanent eye damage.

Insufficient saliva in the mouth can dull taste and smell, make eating and swallowing painful, and cause cavities. The salivary glands in the cheeks (parotids) become enlarged and slightly tender in about one third of people. The mouth may also burn, which may sometimes indicate a complicating yeast infection.

In other people, many organs are affected. Sjögren's syndrome can dry out the mucous membranes lining the digestive tract, windpipe (trachea), vulva, and vagina. Dryness of the trachea and lungs can make these organs more susceptible to infection, leading to pneumonia.

Dryness of the vulva and vagina can make sexual intercourse difficult. The protective sac surrounding the heart (pericardium) may be inflamed—a condition called pericarditis. Nerve, lung tissue, and other tissues may be damaged by the inflammation.

Joint inflammation (arthritis) occurs in about one third of people, affecting the same joints that rheumatoid arthritis affects, but the joint inflammation of Sjögren's syndrome tends to be milder and is usually not destructive. Some people also have severe rheumatoid arthritis or systemic lupus erythematosus.

Lymphoma, a cancer of the lymphatic system, is much more common in people who have Sjögren's syndrome than in the general population.

Diagnosis

Although a sensation of dry mouth or dry eyes is fairly common, a sensation of dry mouth and dry eyes accompanied by joint inflammation probably indicates that the person has Sjögren's syndrome. Various tests can help a doctor diagnose this disorder and differentiate it from other connective tissue disorders that can produce similar symptoms.

The amount of tears produced can be estimated by placing a filter paper strip under each lower eyelid and observing how much of the strip is moistened (Schirmer test).

A person who has Sjögren's syndrome may produce less than one third of the normal amount. An ophthalmologist can test for damage to the eye's surface. More sophisticated tests to evaluate salivary gland secretion may be performed, and a doctor may order scans or a biopsy of the salivary glands.

Blood tests can detect abnormal antibodies, including SS-B, an antibody that is highly specific for Sjögren's syndrome. Often, people with Sjögren's syndrome also have antibodies that are more characteristic of rheumatoid arthritis or lupus.

The erythrocyte sedimentation rate (ESR), a test that measures the rate at which red blood cells settle to the bottom of a test tube containing blood, is elevated in about 7 of 10 people. About 1 of 3 people has a decreased number of red blood cells (anemia) or of certain types of white blood cells (leukopenia).

Prognosis and Treatment

The prognosis is generally good. However, if the lungs, kidneys, or lymph nodes are damaged by the antibodies, pneumonia, kidney failure, or lymphoma may result.

No cure for Sjögren's syndrome is available, but symptoms can be relieved. Dry eyes can be treated with artificial tear drops. A dry mouth can be moistened by continuously sipping liquids, chewing sugarless gum, or using a mouth rinse.

Drugs that reduce the amount of saliva, such as decongestants, antidepressants, and antihistamines, should be avoided because they can worsen the dryness. The drug pilocarpine may help stimulate the production of saliva if the salivary glands are not too severely damaged.

Fastidious dental hygiene and frequent dental visits can minimize tooth decay and loss. Painful, swollen salivary glands can be treated with analgesics. Because joint symptoms are usually mild, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and rest is often sufficient. When symptoms resulting from damage to internal organs are severe, corticosteroids such as prednisone given by mouth can be useful.

 

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« Reply #1 on: October 06, 2006, 05:27:10 pm »

Sjogren's syndrome

Overview

Sjogren's (SHOW-grins) syndrome is a disorder of the immune system often defined by its two most common symptoms — dry eyes and a dry mouth.

Yet Sjogren's syndrome is more than just a simple set of symptoms. It's a disease that often accompanies other autoimmune disorders — rheumatoid arthritis, lupus and others. These rheumatic diseases are marked by inflammation of your connective tissues, and it's common for people with Sjogren's syndrome to also have a connective tissue disorder.

In Sjogren's syndrome, your immune system attacks healthy tissue. The mucous membranes and moisture-secreting glands of your eyes and mouth are usually affected first, resulting in decreased production of tears and saliva. This can lead to problems from difficulty swallowing to dental cavities to light-sensitive eyes to corneal ulcers. Sjogren's syndrome can also result in damage to tissues of your lungs, kidneys and liver.

Although you can develop Sjogren's syndrome at any age, most people are older than 40 at diagnosis. The condition is nine times as likely to occur in women as in men. There's no cure for Sjogren's syndrome, but treatments can relieve many of the symptoms.


Signs and symptoms

Sjogren's syndrome can be difficult to diagnose because the signs and symptoms are similar to those caused by other diseases and can vary from person to person. In addition, the side effects of a number of medications can mimic some signs and symptoms of Sjogren's syndrome. Still, typical signs and symptoms of Sjogren's include:

Dry eyes
Dry mouth
Dental cavities
Fatigue
Fever
Enlarged parotid glands — one particular set of your salivary glands, located behind your jaw and in front of your ears
Difficulty swallowing or chewing
Change in sense of taste
Hoarseness
Oral yeast infections, such as candidiasis
Irritation and mild bleeding in your nose
Skin rashes or dry skin
Vaginal dryness
Dry cough that doesn't produce sputum
Joint pain, swelling and stiffness
Difficulty swallowing
Oral thrush
Causes

Sjogren's syndrome is an autoimmune disorder. This means that your body attacks its own cells and tissues. It's unknown why this happens, but researchers believe that a combination of factors causes something to go wrong with your immune system. These factors may be related to heredity, hormones, a viral or bacterial infection, or your nervous system. In the case of Sjogren's syndrome, white blood cells called lymphocytes target, attack and damage your moisture-producing glands. They can also damage other organs, including your lungs, kidneys and liver.

Sjogren's syndrome that results from a rheumatic condition is classified as secondary Sjogren's syndrome. Primary Sjogren's syndrome occurs by itself.


Risk factors

Although anyone can develop Sjogren's syndrome, it typically occurs in people with one or more known risk factors. These include:

Having a rheumatic disease. It's common for people who have Sjogren's syndrome to also have a rheumatic disease, such as rheumatoid arthritis, lupus, scleroderma or polymyositis.
Being female. Women are nine times as likely as men are to have Sjogren's syndrome.
Being a certain age. Sjogren's syndrome is usually diagnosed in people older than 40.
Having a family history of Sjogren's. Sjogren's syndrome sometimes runs in families.

Rheumatoid arthritis
Lupus
Scleroderma
Polymyositis

When to seek medical advice

Sjogren's syndrome tends to develop slowly. But once symptoms occur they can lead to complications that require medical attention. If you notice such symptoms as unusually dry eyes or a dry mouth that lasts for more than three months, seek medical advice.

How do you know if your eyes are unusually dry? If the dryness persists or if you frequently feel as if you have grit or sand in your eyes, you're probably experiencing unusually dry eyes. Or you may find you're using artificial tears more than three times a day. Important signs and symptoms of oral dryness include daily dry mouth for more than three months or recurrent or persistent swollen salivary glands. If you drink liquids to help swallow dry foods, you may also have an unusually dry mouth.

Keep your primary doctor informed
A diagnosis of Sjogren's syndrome can be missed or delayed if you report only individual symptoms to your dentist or eye doctor. Therefore, it's important to also let your primary doctor know about a symptom or combination of signs and symptoms. If you have a rheumatic disease, such as rheumatoid arthritis or lupus, tell your doctor about any symptoms that may be related to Sjogren's.

Be aware that many medications can cause dry-mouth symptoms, including drugs used to treat high blood pressure, depression and insomnia. In addition, many drugs — such as phenothiazines, tricyclic antidepressants, antispasmodics and medications used to treat Parkinson's disease — can cause symptoms of dryness throughout your body.
If your medications cause you to experience symptoms associated with dryness, ask your doctor whether alternative medications are an option for you.


Screening and diagnosis

To diagnose Sjogren's syndrome, your doctor will most likely ask for a history of your symptoms, including what they are and how long you've had them. He or she will also want to discuss other conditions you may have and medications you're taking. Your doctor may ask about your diet, including the types and quantities of liquids that you drink in a day.

Beyond reviewing your medical history, your doctor can use a variety of tests to diagnose Sjogren's syndrome:

Blood tests. Your doctor may order blood tests to check your blood counts and sedimentation rate and to check for autoantibodies. Checking your blood count lets your doctor know the proportion of the various types of blood cells in a given volume of your blood.

Sedimentation rate refers to the speed at which the red blood cells settle to the bottom of a column of blood in a glass tube. Certain inflammatory conditions increase the sedimentation rate. Autoantibodies can play a role in the inflammatory response, which can damage your tissues and organs.
 
Tear test.
Your doctor can measure the dryness of your eyes with a Schirmer tear test, in which a small piece of filter paper is placed under your lower eyelid to measure your tears. In another version of the Schirmer test, a cotton swab is used to stimulate the tear reflex in your nose. A medical eye doctor (ophthalmologist) may also examine your eyes with a slit-lamp after placing a drop of liquid containing a dye in your eye. The dye stains areas of the cornea that have been damaged by the dryness.
 
Imaging.
To check on the condition of your salivary glands, your doctor may order a special X-ray called a sialogram. It detects dye that is injected into your parotid glands, located behind your jaw and in front of your ears. The dye is injected through the opening of a small duct in your mouth.
This procedure reveals the flow of saliva into your mouth. Your doctor may also perform a parotid gland flow test to determine the amount of saliva that you produce over time. Another imaging test is a salivary scintigraphy, which measures your salivary gland function. Your doctor may also order a chest X-ray to check for lung inflammation.

Biopsy.
Your doctor may also want to do a lip biopsy to detect the presence of clusters of inflammatory cells, which can indicate Sjogren's syndrome. For this test, a small sliver of tissue is removed from salivary glands located in your lip and examined under a microscope.

Urine sample.
Your doctor may want you to provide a urine sample that can be analyzed in the laboratory to determine whether Sjogren's syndrome has affected your kidneys.

Slit-lamp exam.
Your doctor may use magnifying equipment to determine how dry your eye is and whether the outside of your eye is inflamed.


Many of the complications of Sjogren's syndrome are more annoying than serious. But serious problems can develop, especially if you have a rheumatic disease along with Sjogren's syndrome. Common complications of Sjogren's syndrome include:

Difficulty swallowing. Lack of saliva may make it more difficult for you to chew and swallow.
Dental cavities. Because saliva helps protect the teeth from bacteria, you are more prone to developing cavities if your mouth is dry.
Vision problems. Dry eyes can lead to light sensitivity, blurred vision and corneal ulcers.

Less common complications include:

Inflammation of organs such as your lungs, kidneys or liver. Inflammation may cause pneumonia, bronchitis or other problems in your lungs; may lead to problems with kidney function; and may cause hepatitis or cirrhosis in your liver.

Heart problems for babies born to mothers with Sjogren's syndrome. If you're a woman with Sjogren's syndrome and you plan to become pregnant, talk with your doctor about being tested for certain autoantibodies that may be present in your blood.

These antibodies, anti-Ro (anti-SS-A) and anti-La (anti-SS-B), have been associated with a neonatal lupus syndrome, which can cause a rash on your baby that will clear up within a few months. In rare cases this antibody is associated with heart problems in newborns.

Cancer of the lymph nodes (lymphoma). A small percentage of people with Sjogren's syndrome develop lymphoma. Symptoms include swelling of the salivary glands, fatigue, weight loss and night sweats.

Peripheral nervous system disorders. Peripheral neuropathies are common in people with Sjogren's syndrome. Your legs may be especially affected and you may experience symptoms of numbness, tingling and burning. Your cranial nerves — such as those relating to your eyes (optic nerve) or face (trigeminal nerve) — can be affected and may cause visual problems or facial pain.


Treatment

You can relieve many of the symptoms of Sjogren's syndrome with a self-care plan you can develop with your doctor. He or she will likely review the medications that you're taking to be sure they're not contributing to the problem. Your doctor may also prescribe medication to help ease certain symptoms.

Medications
Nonsteroidal anti-inflammatory drugs (NSAIDs). This group of medications, which includes aspirin, helps relieve both pain and inflammation. Your doctor may recommend you take these medications if you have painful or swollen joints. Side effects may include indigestion and stomach bleeding. Therefore, always take NSAIDs with food. Prescription NSAIDs can provide higher doses and more potency than over-the-counter types of NSAIDs.
 
Corticosteroids.
These medications reduce inflammation and may slow joint damage. In the short term, corticosteroids can make you feel dramatically better. But when used for many months or years, they may become less effective and also cause serious side effects. Side effects may include easy bruising, thinning of your bones, cataracts, weight gain, a round face, diabetes and high blood pressure.

Hydroxychloroquine (Plaquenil).
This antimalarial drug may be useful if you have inflamed joints, as with rheumatoid arthritis. It's not usually effective for the dryness caused by Sjogren's syndrome.
 
Pilocarpine (Salagen).
Your doctor may prescribe pilocarpine if you have dry-mouth symptoms caused by Sjogren's syndrome. It's not an option if you have poorly controlled asthma, inflammation of the iris (acute iritis), glaucoma or significant cardiovascular disease, or if you're pregnant or breast-feeding. Pilocarpine may cause increased sweating and headaches.
 
Cevimeline (Evoxac).
This prescription medication also is used to relieve symptoms of a dry mouth. The medication works by causing certain mouth glands to produce more saliva. Common side effects may include excessive sweating, nausea, and a runny or stuffy nose. Less common side effects, for which you should check with your doctor immediately, may include difficulty breathing, fast heartbeat and itching.

Cyclosporine.
Your ophthalmologist may recommend you use eyedrops containing cyclosporine (Restasis) to treat symptoms of Sjogren's syndrome that affect your eyes.
 
Immunosuppressants.
These medications, such as cyclophosphamide (Cytoxan), methotrexate (Rheumatrex), mycophenolate (CellCept) and azathioprine (Imuran), suppress the immune system. Your doctor may prescribe them for you if you develop problems with your lungs, kidneys, blood vessels or nervous system.

Surgery
One way to relieve dry eyes is to undergo a minor surgical procedure to seal the tear ducts that drain tears from your eyes (punctal occlusion). Collagen or silicone plugs are inserted into the ducts for a temporary closure. Collagen plugs eventually dissolve, but silicone plugs will keep ducts sealed until they fall out or are removed. Your doctor may use a laser to permanently seal your ducts.


Self-care

Many symptoms of Sjogren's syndrome respond well to self-care. A self-care plan may mean you follow some of the following advice:

Use artificial tears and eyedrops. These can relieve the discomfort of dry eyes. Artificial tears and eyedrops are available by prescription or over-the-counter. Thicker drops are available that you don't have to apply as often as other drops, but they may cause visual blurring and collect along your eyelashes.

Ask your doctor about whether you should select artificial tears with or without preservatives, because the preservatives used to prolong the shelf life of some products can cause eye irritation in some people.

Another treatment that can keep your eyes moist is small pellets of hydroxypropyl cellulose (Lacrisert), which are placed in your lower eyelid. When you add artificial tears, the pellet dissolves and forms a film over the moisture.

Increase your fluid intake. Drinking lots of fluids, particularly water, helps to reduce dry mouth. Lemon juice in water may help stimulate salivary flow. Sugarless gum or hard candies also may help. Because the risk of dental cavities increases with Sjogren's syndrome, reduce your sugar intake.
 
Use moisturizers. If dry skin is a problem, avoid using very hot water to wash and avoid soaking your hands in water or cleaning solutions. Pat your skin — don't rub — with a towel and apply moisturizers when your skin is still damp. Use rubber gloves when doing dishes or housecleaning.

Vaginal moisturizers and lubricants help women who experience vaginal dryness.

Stop smoking. Avoid smoking or exposure to secondhand smoke because smoke can increase your dryness.

Increase humidity. Increasing the indoor humidity or protecting yourself in windy environments may help you reduce dryness. For example, avoid sitting in front of a fan or air conditioning vent. You may also want to use goggles or protective eyewear when you go outdoors.

Protect your oral health. Brush your teeth after every meal and schedule regular dental appointments to protect against the increased risk of dental cavities. Your dentist or doctor may also tell you to use daily topical fluoride treatments and antimicrobial mouthwashes. Artificial saliva products can help keep your mouth feeling moist. These products can also help to prevent cavities if they contain fluoride.

If you develop an oral yeast infection (such as candidiasis), your doctor may prescribe antifungal lozenges — for example, clotrimazole (Mycelex) — that will slowly dissolve in your mouth. Antifungal medication is also available in liquid form, such as nystatin (Mycostatin), for you to swish around your mouth.

Inflammation of the parotid gland (parotitis) can be helped by massage, the use of warm compresses, and the stimulation of your salivary flow — such as through the use of sugarless lemon drops or other hard candies. NSAIDs may help relieve your discomfort and inflammation.

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« Reply #2 on: October 10, 2006, 02:47:11 pm »

Sjogren's Can Damage Many Organs, Not Just Eyes

While some of the symptoms of Sjogren's syndrome (such as dryness, grittiness, blurred vision and chronic discomfort and pain) may be most obvious in the eyes, the autoimmune disorder can affect organs throughout the body and has been linked to a host of other serious medical problems.

In Sjogren's (pronounced "show-grins"), immune cells attack the cells that produce tears and saliva. Once those cells are destroyed, the tear and salivary glands can't secrete fluid normally because they become infiltrated with lymphocytes (a type of white blood cell). Sjogren's typically occurs in middle-aged women, but has been diagnosed in women of all ages and in men as well. It is difficult to diagnose and there is no cure.

"Sjogren's syndrome is a systemic disease that has many manifestations," said E. Lee Stock, MD, Medical College Professor of Ophthalmology, who practices at the The Eye Institute of the Medical College of Wisconsin and Froedtert Hospital. Sjogren's syndrome is recognized as an autoimmune disease - in which the body mistakenly attacks its own tissue - but the causes of autoimmune disorders are not understood.

"I see quite a few Sjogren's patients here. We try to separate out patients who have isolated dry eyes and patients who have dry eyes related to Sjogren's," explained Dr. Stock. "The problem with Sjogren's is that because it has so many different manifestations it's sometimes not all put together. The patient may have dry eyes and also have a lot of other symptoms, but only the eyes will be looked at. Or they may have dry mouth, but only the dentist will see it."

Patients with dry eyes secondary to Sjogren's need a slightly different approach, since systemic medication for arthritis or other inflammation can alter the signs and symptoms of dry eye.

Painful Symptoms Include Dry Mouth
Dry mouth is another "classic" symptom of Sjogren's syndrome, which can also cause skin, nose, and vaginal dryness and affect the brain. Sjogren's symptoms may develop slowly over several years and in that time other complications often arise. According to the National Institutes of Health, about half of people with Sjogren's go on to develop rheumatoid arthritis, lupus, or lung and kidney problems within five to ten years after diagnosis.

Sjogren's symptoms can be highly irritating and painful. Patients may experience increased sensitivity to light and itching, burning, and redness in the eyes. Dry mouth can increase the incidence of sores and dental cavities, affect taste, and make swallowing dry food difficult. Over-the-counter preparations to enhance eye moisture are available and drinking plenty of fluids provides temporary relief for some symptoms, but these are not cures and do not help with the major systemic problems.

"From my point of view the important thing first of all is to see if they have Sjogren's and then to make sure that they're managed systemically, not just their eyes," said Dr. Stock.

Diagnosis Is Complicated
Dr. Stock noted that there is no single diagnostic test for Sjogren's syndrome. Physicians must rely on their ability to diagnose clinically, based on what can be a complex array of symptoms and medical history information gleaned from each patient.

"It's not simple because of all the manifestations," said Dr. Stock. "For instance, all my patients are asked if they have arthritis or if they have anything dry: dry eyes, dry mouth, dry throat, or vaginal dryness. Sjogren's is first a clinical diagnosis, but there are certain autoimmune antibodies, called SSA and SSB, which may be helpful in diagnosing Sjogren's.

"There have been new developments in treatment recently. For instance, for the eye we have a drug called Restasis (cyclosporin) that potentially can have a basic effect on the chain of inflammation and dryness. In addition it may protect the lacrimal gland. That's a new treatment that's only been out for a few years." Froedtert & The Medical College and the Eye Institute may soon be involved in studies of new artificial tears, said Dr. Stock.

According to the National Institutes of Health, moisture replacement therapies may ease the symptoms of dryness, non-steroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms, and for individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed. But until more is learned about autoimmune disease - the root cause - treatment for Sjogren's syndrome will remain generally symptomatic and supportive.

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« Reply #3 on: October 12, 2006, 01:20:25 pm »


Sjogren's Syndrome and Lupus: What You Should Know


 

Sjogren's syndrome (pronounced SHOW-grins) is a chronic inflammatory disease that can affect many organs of the body. But it most commonly damages the body's moisture producing glands, causing dry eyes and dry mouth. Like lupus, Sjogren's is an autoimmune disease; this means that the body's immune system has run amok - instead of just protecting you from invaders, it is attacking parts of your body as if they were invaders. The parts of the body largely under attack in SS are its moisture-producing glands - such as the salivary glands that produce saliva in your mouth and the glands that produce tears in your eyes. So the most common symptoms are dry eyes and dry mouth (xerostomia). The dryness of Sjogren's is also called sicca.

Types of Sjogren's Syndrome (abbreviated SS)

SS can occur alone (known as primary SS). Or it can occur in conjunction with other autoimmune disorders, such as lupus, rheumatoid arthritis, scleroderma, dermatomyositis, or primary biliary cirrhosis (called secondary SS).

Who gets it?

Research suggests that four new cases of Sjogren's occur per 100,000 people in the population every year, and that 70% of cases are primary SS. But this is likely a low estimate because up to 38% of elderly people report having dry mouth and eyes. However, only 0.04 to 2.7% of elderly meet the full criteria for SS. In addition, Sjogren's is more common in women than in men.

About 20% of people with lupus also have SS. Because some of the symptoms of lupus and Sjogren's syndrome are similar, it can sometimes be difficult to discern which disease is causing a particular problem.

Criteria for SS

When doctors are conducting research on a disease, it's important that everyone in a research trial have disease that is defined in the same way. That's why researchers have developed criteria to define diseases. Criteria are a group of symptoms and signs - the standard by which admission to a research study is measured.

The Revised International Classification Criteria for SS requires the presence of four of the following six factors.

Ocular (eye) symptoms - yes to one or more of these questions:
Have you had daily, persistent, troublesome dry eyes for more than three months?
Do you have a recurrent sensation of sand or gravel in the eyes
Do you use tear substitutes more than three times a day?
Oral (mouth) symptoms - "yes" to one or more of these questions:
Have you had a feeling of dry mouth for more than three months?
Have you had recurrent or persistently swollen salivary glands as an adult?
Do you frequently drink liquids to help you swallow dry foods?
Ocular (eye) tests
Positive results when your doctor gave you the Schirmer's test, which involves placing a small piece of absorptive paper into the edge of your eye and evaluating how much moisture was absorbed after five minutes.
Positive results when your doctor did the Rose Bengal staining test, which involves placing a bit of dye on the eye and assessing the condition of the cornea under a special lamp.
Histopathology (study of cells and tissues)
Positive results of a biopsy of your salivary gland.
Salivary gland involvement - abnormal results on one or more of the following tests:
Parotid scintigraphy - a type of photograph of the glands after a radiation emitting; substance has been injected into it;
Parotid sialography - an X-ray of the glands after dye has been injected;
Unstimulated salivary flow - the amount of saliva you produce.
Autoantibodies (cells in the blood that attack your own tissue) - one or more of the following:
Antibodies to Ro/SSA or La/SSB;
Antinuclear antibodies;
Rheumatoid factor.
All criteria agree that you don't have Sjogren's if you already have lymphoma, graft-versus-host disease, AIDS, hepatitis C -- diseases that can cause similar symptoms.

However, remember that these are the criteria used in research studies. In clinical practice, your doctor may diagnose SS based solely on your symptoms, physical examination and blood tests without requiring invasive testing.

Symptoms of Sjogren's

The severity of SS can range from mild to quite debilitating. Some people only have mild to severe dry eyes and mouth. Others may have a wide range of symptoms including (listed in decreasing order of frequency):

mucous-like strands in the eyes, especially in the morning, due to abnormalities in the tears;
difficulty swallowing dry foods due to lack of saliva
enlargement of the salivary glands;
dryness in the nose and throat, leading to a dry cough;
vaginal dryness;
candida (yeast infection) of the mouth (thrush) or vagina;
skin rashes, including purple spots;
fatigue;
pain in the joints (in approximately 50% of patients)
muscular weakness or pain;
color changes in the fingers or toes when exposed to cold or emotional stress (Raynaud's phenomenon) (in about 35% of patients)
inflammation of blood vessels (vasculitis)- rare (in only 5% of patients)
shortness of breath or other difficulty breathing;
nausea, stomach pain, or indigestion due to gastritis;
yellow eyes or skin (jaundice) or skin itching, when it coexists with liver disease;
neurological symptoms, including abnormal sensations or movements, hearing loss, double vision, drooping on one side of the face (Bell's palsy), dizziness, or psychiatric symptoms.
The Importance of Diagnosis

Any such symptoms should be reported to your doctor promptly. It could be Sjogren's - or it could be something else. For example, eye symptoms could also be due to contact lens use, a dysfunction of your corneal nerve, inadequate vitamin A, or other problems. Dry mouth can also be caused by a wide range of drugs (such as antidepressants, antihistamines, and diuretics), other diseases (such as poorly controlled diabetes), as well as anxiety. Indeed, any symptom that "looks like" SS could have another cause - some mild and easily treatable and others very severe.

It's important that SS be diagnosed not only because you want treatment for the symptoms but also because your doctor will watch for problems associated with Sjogren's more carefully. For example, although not common, SS increases your risk for kidney, liver, thyroid, lung, and blood and blood vessel problems as well as, rarely, lymphoma. (A 1998 study suggested that only about 3% of people with Sjogren's develop lymphoma.). Despite all these risks, the overall lifespan of people with primary SS is similar to that of people without the disease.

Your dentist also needs to know if you have Sjogren's in order to participate in your therapy and provide preventive treatment. For example, people with SS are more likely to develop cavities and gum disease due to the shortage of saliva - and more likely to have their fillings fall out and their bondings fall off.

In addition, if you have surgery, your surgeon and anesthesiologist need to know about your Sjogren's. Because operating rooms have low humidity, you will need to have an eye lubricant before the procedure to reduce your risk of damage to the cornea of the eye; bring your own eye ointment with you. Because of dry mouth and dental problems, your anesthesiologist will take special protective steps too.

Treatment

More than 90% of Sjogren's patients can be treated with simple and effective measures, most of which involve self-help but some of which require a doctor's prescription or a procedure. The Moisture Seekers newsletter of the Sjogren's Syndrome Foundation can be particularly helpful; call (800) 475-6473 or visit their website www.sjogrens.com.

Your doctor will try to avoid prescribing drugs that may worsen your symptoms of dryness, and you should avoid non-prescription antihistamines. In addition, try these tips.

For dry mouth: Stimulate your existing saliva by sucking on sugarless candies or dried fruit slices, chewing sugar-free gums, or sucking citrus-flavored sugarless tablets (such as Salix SST). Take frequent small sips of water. Try using artificial saliva preparations, such as Oral Balance, Moi-Stir, Mouthkote, Optimoist, Salivart, Orex, and Salix lozenges. If you don't see them on your pharmacist's shelves, ask for a special order. If medication is necessary, your doctor may prescribe pilocarpine (brand named Salagen) although it may cause increased sweating and urination and flushing or abdominal pain in some people, or cevimeline (Evozac), although it can't be used by people with uncontrolled asthma or narrow angle glaucoma.

Whatever your dry mouth treatment, you also need meticulous dental care. Try Biotene toothpaste to help prevent mouth irritation. Ask about fluoride solutions and gels; if you develop rapidly progressing dental disease, fluoride can be applied directly to the teeth from plastic trays worn at night. Consider using an electric toothbrush, such as Sonicare, especially if you have gum disease or have joint pains that make regular brushing uncomfortable. Floss daily. Dentures should be disinfected overnight with chlorhexidine solution 0.2% to help avoid infection with candida.

For dry eyes: Use artificial tears throughout the day and an opthalmic ointment at night. To prevent air from drying your eyes, try wrap-around sunglasses or side shields can be fitted to your glasses; ask your eye doctor about Moist Eye Moisture Panels. (You can see them at http://www.eaglevis.com/products.htm.) Or try ski or swim goggles. If none of this works, your eye doctor can do a procedure called punctal occlusion in which tiny (removable) plugs are placed in the tear ducts of your eyes to slow the drainage of tears.

Try to avoid low humidity situations (air conditioning, central heating, airplanes, windy locations) or use extra eye drops in these situations. If the air in your home is dry, use of a humidifier may be helpful. Also try to avoid irritants such as dust and cigarette smoke.

For dry skin: Dry skin can be treated with moisturizing lotions and bath additives.

For vaginal dryness: Lubricants, such as K-Y Jelly, add moisture, while Replens helps retain your own moisture longer.

For systemic disease: If your symptoms go beyond your eyes and mouth, your doctor may recommend an oral drug. Depending on the severity of your SS, one or more of the following might be prescribed: hydroxychloroquine (brand named Plaquenil and particularly useful for joint pain), prednisone, methotrexate, azathioprine, cyclosporine or cyclophosphamide. Current research is also exploring investigational therapies, including: oral interferon-alpha lozenges and an intravenous drug used to treat rheumatoid arthritis called infliximab (Remicade). However, infliximab cannot be given to people who have lupus, because it might worsen their disease.

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« Reply #4 on: December 29, 2006, 07:58:39 pm »


What is Sjogren's Syndrome?

Sjogren's Syndrome (SS) is a disease in which the lacrimal and salivary glands are chronically inflamed. This causes deficient tear and saliva production with possible complaints of dry eyes and dry mouth. When it occurs by itself it is called primary SS. If it occurs as a part of another autoimmune disease it is called secondary SS. SS can be considered a point where all the autoimmune diseases meet. Which means that a lot of autoimmune diseases have SS in common. In SS overactive immunological cells (lymphocytes) may turn out to be malignant. Fortunately this is rarely the case. This is why SS is considered an important link between autoimmunity and malignancy.
 
Prevalence
SS is not a rare disease. It follows rheumatoid arthritis in number, which is a very common disease. Ninety percent of the patients are females and although it can occur at all ages, the onset of the disease is usually situated round the menopause (at 43 years on average). Familial types also occur.
 
Most important symptoms
Primary SS
In primary SS first complaints are usually dry eyes or dry mouth, which can be very disturbing. Dry eyes feel sandy or gritty. In the morning, the eyelids may stick together or the eye sight may be blurry due to a film of dried out tears on the eye. Occasionally small wounds caused by insufficient tear production occur on the eye. A dry mouth makes speaking and eating very difficult. Patients need to drink a lot to be able to swallow food. They often complain about pain in the mouth. Caries form more easily and dental prostheses are hardly tolerated, do not stay on and sometimes cause pain. Swollen salivary glands, and especially swollen parotid glands occur occasionally. Only rarely is the swelling very extreme.
 
Secondary SS
Secondary SS will often be discovered after other diseases like lupus or rheumatoid arthritis have been diagnosed. Laboratory test results may be abnormal without the patient experiencing complaints. Increased production of antibodies, the production of autoantibodies (especially anti-La and anti-Ro), a low amount of white blood corpuscles and the presence of the rheumatoid factor are typical.
 
Diagnosis
Dry eyes and/or mouth together with one or more significant abnormality in lab tests are sufficient to make a diagnosis.
In case of doubt, a lip biopsy, by means of which small salivary glands are examined, may be helpful to determine the diagnosis of Sjogren's Syndrome. Since practically all biopsies show abnormalities, however, it is not a reliable test to diagnose Sjogren's Syndrome. A lip biopsy heals slowly and may leave a scar. It may also be painful.
In a sialography contrast-fluid is injected in the salivary duct. This is quite a difficult and disagreeable test and it is rarely used.
A scintigraphy is less complicated and is more comfortable for the patient. A radioactive substance is injected into the blood. It accumulates in the salivary glands and is secreted together with the saliva. In this way, the functioning of the salivary glands can be measured. The ophthalmologist can measure the production of tears by means of the Schirmer test (a slip of paper absorbs the tears) or by means of colouring agents.
 
Involvement of other organs in SS
I In secondary SS all symptoms of the accompanying connective tissue disease may be present.
Organ involvement is also often found in primary SS:
Dryness of the bronchial tubes causing a tickling cough
An invasion of lymphocytes (immunologically active cells) may inflame the connective tissue in the lungs. Foci (points of lodgement and development) of these cells may provoke a dry cough or shortness of breath
A dry mouth or throat may cause swallowing difficulties, but are rarely provoked by involvement of the upper part of the oesophagus
Reduced secretion of gastric juice occurs but is seldom the source of complaints, although it may evolve into a type of anaemia
Secretion of the pancreas may be reduced, mostly without observable consequences
The liver may show signs of autoimmune involvement; primary biliary cirrhosis or chronic hepatitis
Kidney involvement usually causes insufficient urine concentration (with nocturia, i.e. urinating at night, as a result) or acidosis, a slight souring of the blood
Purpura (subcutaneous bleedings) are rare
Joint pain, mostly with swelling, occurs in two out of three patients
Involvement of the central nervous system may occur with neuralgia in the limbs, and rarely causes severe damage to the spinal cord or brain. Psychiatric complaints are common: mostly depression, but also concentration problems, difficulties to memorise, personality changes and sleep disorders
Allergies to medication are very common in SS
Hyperviscosity seldom occurs. This happens when the blood becomes thicker due to too many antibodies (sometimes also rheumatoid factor) in the blood. Symptoms may vary: mostly headaches, blurry vision, confusion, nose bleeds and bruises. It is a serious problem that requires immediate treatment with plasmapheresis followed by corticosteroid treatment.
Extreme and sometimes sudden fatigue

 
Autoantibodies 
Autoantibodies are directed against cell components and more specifically against the nuclei of cells. That is why they are called antinuclear (nucleus = centre) antibodies (ANA) or antinuclear factors (ANF).
The ANA test is performed in a lab by adding a fluorescent dye to the blood serum. In this way, antinuclear antibodies can be detected under a microscope. Antinuclear antibodies are present in 40 % of the patients.
Further examination shows primarily a pattern of antibodies against one specific group of cytoplasmatic antigens, especially against La/SSB and Ro/SSA. More specialised techniques could enable the detection of these antibodies in a larger number of patients.
 
Treatment
Dry eyes are best treated with artificial tears.
A dry mouth is difficult to treat. Sucking sour candies and sugar-free chewing gum may give some relief. Drinking lots of water is not recommendable because it flushes away the little saliva and water cannot serve as a substitute for saliva. Sulfarlem or Bisolvon are worth trying. A humidifier may prove useful.
In severe cases low to moderate doses of corticosteroids may help, but high doses are seldom necessary.
 
Heredity 
SS is not hereditary. The disease, however, is believed to possess an inherited susceptibility. There is connection between the HLA DR3 type and the DRw52 type. Although the exact role in the development of SS is still unknown, these HLA antigens (HLA stands for Human Leukocyte Antigen) are believed to be important for the production of autoantibodies. 

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« Reply #5 on: April 24, 2007, 06:31:39 am »

Classification and diagnosis of Sjögren's syndrome


 

 INTRODUCTION — Sjögren's syndrome (SS) is a chronic inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, especially the lacrimal and salivary glands. SS can exist as a primary disorder or as a condition in association with another well defined autoimmune process such as rheumatoid arthritis, systemic lupus erythematosus (SLE) or scleroderma. Its genetics and clinical features most closely resemble a subset of SLE patients.

 

Although primarily  characterized by a particular form of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia), this condition may affect a wide variety of organ systems including skin, lung, heart, kidney, neural and hematopoietic system. SS has many features in common with SLE, but also has certain distinct types of organ involvement such as hyperglobulinemic purpura, renal involvement due to interstitial nephritis, and an increased risk of lymphoma. In this regard, primary SS patients straddle the fence of "aggressive" lymphocytes that infiltrate tissues throughout the body in addition to their infiltration of the lacrimal/salivary glands.

 

At the other end of the diagnostic spectrum is the patient with symptoms of dry eyes, dry mouth, a low titer positive antinuclear antibody, and vague symptoms of fatigue, myalgia and cognitive dysfunction. Distinguishing patients with primary SS from those with fibromyalgia, and depression who have complaints of ocular and/or oral dryness (often exacerbated by medications with anti-cholinergic side effects) has been a challenge confronting those who develop classification criteria, conduct therapeutic trials, and provide clinical care.

 

HISTORY — The first description of SS is generally credited to Johann Mikulicz who, in 1892, described a 42 year old farmer with bilateral parotid and lacrimal gland enlargement associated with a small round cell infiltrate [1]. Because the term "Mikulicz's syndrome" could encompass so many different entities including tuberculosis, other infections, sarcoidosis, and lymphoma, the term "Mikulicz syndrome" fell into disuse because it did not provide sufficient prognostic or therapeutic information .

The term is still occasionally used to describe the histologic appearance of focal lymphocytic infiltrates on salivary gland biopsies. In 1933 the Danish ophthalmologist Henrik Sjögren described clinical and histologic findings in 19 women, 13 of whom had probable rheumatoid arthritis, with dry mouth and dry eyes. Sjögren introduced the term "keratoconjunctivitis sicca" (KCS) for the latter syndrome to distinguish it from dry eyes caused by lack of vitamin A ("xerophthalmia").
 In 1953, Morgan and Castleman presented a case of Sjögren's syndrome in a clinical pathologic conference and rekindled interest in the symptom originally known as "Mikulicz's syndrome" and later termed Sjögren's syndrome [3]. The clinical features of the disease as we currently recognize the syndrome in its overt form were outlined in 1956 by Bloch et al .There has been considerable debate about the classification criteria with milder forms of SS that are discussed below.

 

However, the basic issue of diagnostic difficulty present in 1956 continues until the present. In the absence of a characteristic etiologic agent, the syndrome is defined by its clinical and laboratory features. The ocular component (aqueous tear deficiency or keratoconjunctivitis sicca) is well defined by its clinical signs. However, quantitation of the oral component of dry mouth has been more difficult since symptoms of dryness are common and most physicians/patients are reluctant to recommend/undergo minor salivary gland biopsy..
 Perhaps because of the infrequency of with which biopsies are performed, tissue obtained may be inadequate, and pathologists not experienced in reading these samples may incorrectly interpret the findings .Although laboratory tests such as antinuclear antibodies (ANA) have proved helpful in diagnosis, the ANA are much more sensitive than they are specific .These issues remain the core of the diagnostic dilemma surrounding SS.

 

AMERICAN-EUROPEAN CLASSIFICATION CRITERIA — Classification criteria for use in scientific communication and clinical research have evolved. Criteria have been proposed by a group of American and European rheumatologists to serve as international criteria for classification of SS [9,10]. These criteria were not developed for use in routine clinical practice and not every patient who receives a clinical diagnosis of SS will fulfill the proposed criteria .


 

These consensus criteria combine subjective symptoms of dry eye and dry mouth with objective signs of xerophthalmia (Schirmer's test, Rose Bengal or lissamine green staining) that can be easily performed at the time of the examination. Although the ophthalmologist may be best suited to perform these in conjunction with slit-lamp examination, these tests can be done without biomicroscopy.
Additional confirmatory tests for oral dryness require laboratory evaluation. However, the requirement in the consensus criteria for either a characteristic minor salivary gland biopsy or a characteristic autoantibody (such as anti-Sjögren's syndrome-A antibody [anti-Ro/SSA] and anti-La/SSB) help distinguish the dryness of SS from other causes of dryness.

 

 Criteria — The consensus criteria are divided into six "items" . Each item has a set of from one to three defining criteria. An item is considered present if any one of the criteria included in its set is present. The "items" are the following:

 

  •  Ocular symptoms of inadequate tear production

  •  Oral symptoms of decreased saliva production

  •  Ocular signs of corneal damage due to inadequate tearing

  •  Salivary gland histopathology demonstrating foci of lymphocytes

  •  Tests indicating impaired salivary gland function

  •  Presence of autoantibodies (anti-Ro/SSA, anti-La/SSB, or both)

 

  Ocular symptoms — The presence of dry eyes may be sought with questions such as: "Do you often feel a gritty or sandy sensation in your eyes?"
 or "Have you had daily, persistent troublesome dry eyes for more than three months?".Keratoconjunctivitis sicca is one cause of dry eyes. It is characterized primarily by a deficiency in aqueous tear production; other causes result from mucin deficiency (eg, due to lack of vitamin A), blepharitis due to Meibomian gland dysfunction, or excessive evaporation from the ocular surface (as in working for many hours in front of a computer monitor in a low humidity environment) .
Use of a tear substitute more than three times daily, even in the absence of complaints of ocular dryness, is acceptable to meet the criterion of having symptoms of dry eyes.

 

  Oral symptoms — The presence of dryness of the mouth and oral cavity may be revealed by questions such as "Do you wake up at night feeling so dry that you have to drink water?" or "Do you frequently drink liquids to aid in swallowing dry foods?" .

 

  Objective evidence of dry eyes — Tear production may be measured using the Schirmer test. A small piece of sterile filter paper, which comes in a standard Schirmer test kit, is placed in the lateral third of the lower eyelid and the extent of wetting in a given time is measured . Wetting of less than 5 mm in five minutes is considered abnormal. Use of topical anesthesia and blotting of the tear reservoir prior to the test may improve accuracy as a measure of basal tear production. The amount of wetting is typically symmetrical.

 

End organ damage to conjunctival and corneal epithelial cells may be measured by Rose Bengal, which stains areas of devitalized tissue. 10 µL of 1 percent Rose Bengal is instilled into the inferior fornix of the unanesthetized eye, the patient blinks twice, then the extent of staining of conjunctiva and cornea is scored .Scoring damage in three regions of the eyes requires slit lamp examination, although some measure of staining can be obtained with an ophthalmoscope.

 

Other tests include the measurement of tear film instability by measuring breakup time after instillation of fluorescein, and measurement of tear osmolality as an indication of evaporation from the ocular surface .Tear film breakup, like Rose Bengal staining, requires slit lamp examination and both are therefore more likely to be performed by ophthalmologists.

 

  Salivary gland biopsy — A labial salivary gland biopsy (LGB) can be an important diagnostic tool in patients with suspected SS. The biopsy should be taken from a macroscopically normal, nontraumatized part of the lower lip and should be large enough to contain at least four lobules. The key histologic feature is focal collections of lymphocytes, often beginning centrally within the lobule. The most widely accepted grading system records the number of foci of lymphoid tissue, defined as collections of 50 or more lymphocytes per 4 mm2 [17,18]. Most criteria require more than one focus per 4 mm2 for a definitive diagnosis of SS. Immunocytology shows most of the lymphocytes are CD4+ T cells 2


 

There is some disagreement about the specificity and sensitivity of LGB for SS .Some patients with apparently classic SS do not show typical histology, a problem that may be due to sampling error. On the other hand, SS-like findings have been reported in other connective tissue disorders and in normal elderly subjects. Quantitative immunohistology may improve the specificity for SS .Another approach to improve the accuracy of LGB is to calculate a cumulative focus score by examining several sections separated by at least 200 µM .When compared to a focus score calculated from one section only, the multisection approach improved specificity of LGB from 84.5 percent to 94.4 percent without any change in sensitivity (93.9 percent).

 

Certain pathologic features, such as parenchymal atrophy and fibrosis, sometimes with scattered lymphoid cells, are almost universal in the elderly and thus, should be excluded from any set of diagnostic criteria for SS. However, as long as focal collections of lymphocytes rather than diffuse scatterings are considered, most authors believe LGB to be the most specific method of confirming the diagnosis of SS  and, hence, the closest we have to a "gold standard."

 

Indications for performing a lip gland biopsy depend upon the patient population and the availability of expert biopsy and histopathology services .Indications for LGB  might include:

 

  •  Confirmation of a suspected diagnosis of SS, especially when it is critical to make the diagnosis as, for example, when systemic or extraglandular features are present

 

  •  Exclusion of other conditions that can cause xerostomia and bilateral gland enlargement

 

The pathology report should document an adequate number of evaluable intact lobules (at least 4) in the specimen, and the average focus score is optimally based on examination of at least 4 lobules [26]. Lobules that have been ruptured due to non-immune mechanisms (eg, sialadenitis [inflammation of salivary gland], leading to rupture of ducts that release mucus), need to be discarded from the quantitation of the focus score .

 

  Objective evidence of salivary gland involvement other than biopsy — To satisfy this item for salivary gland involvement an abnormal result of one of the three following tests is required: technetium excretion radionucleotide scanning (salivary gland scintigraphy), parotid sialography, or unstimulated production of saliva (whole sialometry < 1.5 mL per 15 minutes).

 

  •  Salivary gland scintigraphy — Quantitative salivary gland scintigraphy which gives a dynamic picture of the function of all major salivary glands. The finding of very low uptake of the radionuclide, to the extent that discharge of tracer via the salivary ductal system can not be assessed, is a highly specific for SS but relatively insensitive finding (present in about one-third of SS patients) using this technique .Potential drawbacks to the use of salivary scintigraphy are lack of experience in performing and interpreting the test results and the inability to perform the test in the office setting.

 

  •  Parotid sialography — Parotid sialography is performed by retrograde cannulation of the major salivary gland ducts followed by instillation of an oil based contrast material. Although this method gives excellent visualization of the ducts (including a punctate sialadenitis), it is limited by the risk of rupturing the duct and should not be performed during an episode of acute parotitis .A comparison of parotid scintigraphy and retrograde sialography suggests that the former method has better correlation with parotid function .
Interpretation of sialography requires both training and experience. Unless someone with expertise in performing and interpreting sialography is available, another objective test of salivary gland integrity and/or function is preferred.

 

  •  Sialometry — Sialometry is the measurement of the rate of saliva production. The unstimulated whole salivary flow rate is a relatively simple test and avoids the need for special equipment or agents (such as citric acid) that are used for testing stimulated flow, or the production of saliva by just one parotid gland.

 

The patient is asked to expectorate once, then to collect all saliva into a graduated container. After 15 minutes the volume of saliva is measured. A collection of  < 1.5 mL during this time is abnormally low.

 

  Exclusion criteria — Patients who would otherwise fulfill the classification criteria, are excluded if one of the following disorders is present :

 

  •  Prior head and/or neck irradiation

  •  Infection with hepatitis C virus

  •  Acquired immunodeficiency disease (AIDS)

  •  Pre-existing lymphoma

  •  Sarcoidosis

  •  Graft versus host disease

  •  Recent use of drugs with anticholinergic properties

 

  Rules for classification — The American-European consensus proposed rules for classification of patients based on the criteria are as follows :

 

  •  Primary Sjögren's syndrome — For patients with no associated connective tissue or autoimmune disease (eg, RA, SLE) and no exclusionary diagnoses a classification of primary SS is made according to the consensus rules in one of the three following ways :

 

1. The patient has either a positive salivary gland biopsy result or autoantibodies, and satisfies a total of 4 of the six items (sensitivity 97 percent, specificity 90 percent).

 

2. Alternatively, the patient satisfies three of the four objective items (ocular signs, biopsy, salivary gland involvement, or autoantibodies). This rule had sensitivity of 84 percent and specificity of 95 percent.

 

3. Finally, a classification tree with sensitivity of 96 percent and specificity of 94 percent can be used to determine whether or not patients  are classified as having primary SS.

 

  •  Secondary Sjögren's syndrome — A classification of secondary SS is made according to the consensus rules if a "well defined" connective tissue disease is present and at least one symptom item (indicative of ocular or oral dryness) and any two of the three objective items exclusive of autoantibodies (ie, ocular signs, biopsy, or tests of salivary gland involvement other than biopsy) are present.


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« Reply #6 on: November 04, 2009, 12:57:32 pm »

SJOGREN’S SYNDROME: Support group, 11 a.m. the second Wednesday of the month, Pardee Health Education Center, Blue Ridge Mall, 1800 Four Seasons Blvd., Hendersonville. Call 687-2821.
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« Reply #7 on: November 10, 2009, 10:12:12 am »

Diagnostic Technique Shows Promise for Primary Sjögren’s Syndrome

For the thousands of Americans who will be evaluated this year for the autoimmune disorder primary Sjögren’s syndrome, their doctors will likely test for two antibodies that are often associated with the condition. The problem is today’s standard blood tests detect the more strongly associated antibody, called SSB, only about half the time, making the meaning of a negative result uncertain.

But these numbers could one day improve. Scientists at the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health, report online in the journal Autoimmunity that a rapid, automated test now under development called LIPS identified the SSB antibody correctly three out of four times and with perfect accuracy. It also detected a second antibody, SSA, about as well as today’s standard assays in the group’s initial study of 82 people, 57 of whom had well-characterized primary Sjögren’s syndrome.

“This is just step one in our work to improve antibody detection for Sjögren’s syndrome,” said Peter Burbelo, Ph.D., lead author on the paper and a scientist at NIDCR. “With further refinements, the percentages will only get better.”

Burbelo and colleagues also reported using LIPS to profile additional antibodies of interest that may be related to other largely unrecognized manifestations of the syndrome. These first-pass antibody profiles have the potential to help scientists define for the first time a range of clinical subtypes of primary Sjögren’s, which could greatly improve diagnoses and possibly better target treatment.

Primary Sjögren’s syndrome is a chronic autoimmune disorder that affects about 4 million Americans, 90 percent of whom are women. Scientists have long thought the syndrome is triggered when white blood cells mistakenly attack the body’s moisture-producing glands, typically causing chronic dry mouth, dry eyes, and arthritis.

But other Sjögren’s-related health problems continue to be reported in the medical literature, including lymphoma, thyroid dysfunction, painful peripheral neuropathy, and gastrointestinal problems. These seemingly phantom symptoms remain poorly defined, diagnostically controversial, and suggest a more systemic and yet-to-be-defined underlying pathology.

That’s where LIPS enters the picture. Short for luciferase immunoprecipitation technology, LIPS is a traditional bait-and-bind diagnostic assay. The bait is any recombinant laboratory-made antigen, or segment of a protein known to elicit an antibody response, that is then fused to an enzyme similar to the light-producing luciferase that produces the flash in fireflies.

According to Burbelo, this hybrid antigen is incubated in solution with a drop of a person’s serum. If the antibody of interest is present, it will bind to the bait. Thereafter, the entire antibody-antigen complex attaches to small beads that are then measured by its firefly-like light emission. The greater the intensity of the light flash, the more target antibody there is bound to the antigen.

What makes LIPS different from other antibody tests is its extreme sensitivity, or ability to correctly detect an antibody of interest. Burbelo said this stems from selecting mammalian cells and its biological machinery as the recombinant cloning vector to make the antigens. They more closely resemble human cells than the non-mammalian sources typically used today to make test antigens, such as the bacterium E. coli.

“Antibodies must see the natural three-dimensional shape of an antigen to recognize it,” said Burbelo. “With today’s tests, the assumption is an antigen’s three-dimensional shape will be retained once it’s produced and affixed to plastic. But typically that’s not the case. Antibodies will recognize a stretch of amino acids here and maybe there. They won’t see other pieces of the protein that have degraded and lost their natural conformations.”

“With LIPS, more of the three-dimensional shape is retained, and that heightens the sensitivity,” he continued. “For example, an ELISA [Enzyme-Linked ImmunoSorbent Assay] typically has a dynamic range of between 5 and 15,000 units of signal. A unit of signal is the measure of light intensity. In other words, how bright is the test’s green or red signal? With LIPS, we see samples that range from zero to sometimes over a million units of signal.”

This zero-to-million diagnostic window allows Burbelo and colleagues to more objectively measure any antibody response associated with an autoimmune disorder. It also suggests LIPS may have the potential to detect most developing autoimmune disorders before they become symptomatic, more closely monitor the ups and downs of a patient’s antibody counts over time, and track the immunological outcome of an autoimmune treatment.

To date, Burbelo and colleagues have published intriguing data involving LIPS and a range of autoimmune conditions, from type I diabetes to herpes simplex virus. In the current study, they began by applying their new tool to the Sjögren’s-associated antibodies, SSA and SSB. But they did so with a diagnostic twist.

“Traditionally, the SSA antigen consists of two proteins — Ro52 and Ro60 — that are conjoined and anchored on the plastic diagnostic assays,” said Mike Iadarola, Ph.D., an NIDCR scientist and senior author on the study. “We teased apart the two proteins to present their full three-dimensional shape and were able to measure the antibody response to each separately.”

The group found that 42 of the study’s 57 previously diagnosed Sjögren’s patients had antibody reactions against a segment of the Ro52 antigen that does not elicit a response in today’s ELISA tests, a sign of the LIPS assay’s greater sensitivity. Overall, LIPS detected antibody responses against each protein in about 60 percent of patients, roughly equal to an ELISA, but with a far greater dynamic range and perfect specificity.

The scientists then decided to test for other conditions not traditionally linked to Sjögren’s syndrome but that occasionally — and bewilderingly — have been reported in some patients. “We hypothesized that if we made antigens for the thyroid, stomach, and peripheral nervous system, LIPS could pick out the subset of patients with antibodies against these tissues,” said Iadarola.

And it did. The scientists found 14 percent of their Sjögren’s patients had antibodies against the thyroid antigen, 16 percent had antibodies against an antigen associated with autoimmune gastritis, and four percent had antibodies linked to an autoimmune attack of the eye’s peripheral nerve.

These findings suggest that LIPS may be used as a substitute for more invasive and expensive procedures typically used to diagnose these peripheral conditions. “Again, this study is just a start,” said Burbelo. “All of these tests can be performed on the automated robotic machine in my laboratory, and we can do thousands a day. There’s more data to come.”
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