CLINICAL CONSULT: Advice on Patient Management and Education
Desperately Seeking Saline
What every optometrist needs to know about Sjögren's syndrome.
By Ernie Bowling, O.D., M.S., F.A.A.O., Summerville, Ga.

"Dry eye, dry mouth and possibly also arthritis." This was the mnemonic device I used to remember Sjögren's syndrome on the board exam. Of course, there's a lot more to Sjögren's, and we need to recognize this.

"Optometrists could be the first healthcare providers to direct patients toward a diagnosis of Sjögren's syndrome," says Alexis Stegemann, executive director of the Sjögren's Syndrome Foundation. "By asking dry eye patients questions about other symptoms, such as 'Do you also have dry mouth?' or 'Have you suddenly experienced rampant tooth decay?' optometrists could be a key in early diagnosis."

While dry eye may bring patients to us, the disease affects their bodies in different ways and can test our diagnostic abilities. Here's what you need to know. What is Sjögren's syndrome?

Sjögren's syndrome is a chronic autoimmune disorder in which the body's immune system mistakenly attacks its own moisture-producing glands.

"On the simplest level, Sjögren's syndrome is an inflammatory disease in which T lymphocytes become overactive and cause inflammatory cells to attack the exocrine glands," says Dr. Robert S. Lebovics, an otolaryngologist and chief of Ear, Nose and Throat at Cabrini Hospital in New York City.

Lymphocytes infiltrate and destroy these glands, causing decreased production of tears and saliva. The hallmark symptoms of Sjögren's syndrome are dry eyes and dry mouth. Sjögren's syndrome can also cause dryness of the skin, nose and vagina and can affect other organs of the body. Debilitating fatigue and joint pain from the disease can impair a patient's quality of life.

Sjögren's syndrome is categorized into two forms: primary and secondary.

• Primary Sjögren's. When it occurs alone, without another connective tissue disease, it's called primary Sjögren's. A diagnosis of primary Sjögren's requires both measurable keratoconjunctivitis sicca (KCS) and a positive lip biopsy for invasive lymphocytes. No other connective tissue disease or rheumatoid arthritis is present.

• Secondary Sjögren's. In secondary Sjögren's, the disorder coexists with other autoimmune diseases -- most commonly rheumatoid arthritis, but also systemic lupus erythematosus, scleroderma, polymyositis and polyarteritis nodosa.

A diagnosis of secondary Sjögren's requires connective tissue disease plus either KCS or a positive lip biopsy. Immunogenic, autoantibody and clinical differences exist between the two forms (see Distinguishing Primary and Secondary Sjogren's Syndrome.)

The two forms are evenly split in occurrence rate. Some studies show that patients with primary Sjögren's have more severe dry eye and dry mouth symptoms.

Who gets it, and why

An estimated 4 million Americans have Sjögren's syndrome. Many go undiagnosed.

Nine out of ten Sjögren's patients are female. The reason for the sex disparity is unknown.

Sjögren's syndrome also appears to increase in frequency with age. Normal aging may shrink the tear glands and decrease tear production, but research indicates that aging doesn't cause a decrease in salivary gland production. While most diagnosed women are of menopausal age or older, the disease may occur in children, teenagers and young adults. The causes of Sjögren's syndrome aren't known, but multiple factors are probably involved. These factors include the following:

• genetic factors

• viruses

• hormones

• a combination of all these.

Approximately 12% of patients have one or more relatives, usually female, with the disorder.

What are the symptoms?

No two people will present with the same symptomatology or medical history. Symptoms may plateau, worsen or go into remission. For some, the manifestations are chronic dry eye and dry mouth, while others have cycles of good health followed by severe bouts of disease. See "Signs and Symptoms" 

Diagnosis

Diagnosis is often difficult because the symptoms of Sjögren's syndrome can mimic other diseases such as lupus, rheumatoid arthritis or chronic fatigue syndrome. Because different symptoms may be reported to different specialists, the diagnosis is often missed.

New guidelines have just been clarified, however, which may make diagnosis easier.

"Criteria have been validated in Europe and are near acceptance internationally," says Dr. Steven Carsons, chief of the Division of Rheumatology, Immunology and Allergy and Director of the Rheumatoid Arthritis and Sjögren's Center at Winthrop-University Hospital in Mineola, New York. These criteria consist of six facets:

• ocular symptoms

• oral symptoms

• ocular signs

• oral signs

• presence of antibodies

• minor salivary gland biopsy.

If the patient meets four criteria , this indicates Sjögren's syndrome. However, no criteria set is perfect. We need to be fully cognizant of Sjögren's. Ask more directed questions, and probe for symptoms and signs when taking patient histories.

Testing, testing

Tests you routinely perform can serve as diagnostic tools. They include:

• The Schirmer's test (5 mm wetting in 5 min.) or phenol red thread test (less than 10 mm wetting in 15 seconds) measures tear production.

• Rose bengal and lissamine green staining with a slit lamp evaluation are essential to evaluate corneal or conjunctival dryness. Punctate corneal and/or conjunctival fluorescein or rose bengal staining usually present in the intrapalpebral area. You may find excess mucus and corneal debris in the tear film.

• Sodium fluorescein staining of the precorneal tear film is necessary to determine tear break-up time, an essential test for dry eye. Limit tear break-up time to no longer than 10 seconds. The photo on page 100 shows an eye with KCS demonstrating typical intrapalpebral staining.

• You can also order blood tests for two groups of antibodies, anti-Ro/SS-A and anti-La/SS-B. However, not everyone with Sjögren's will test positive.
  While anti-Ro/SS-A antibodies occur in 60% to 70% of Sjögren's patients, they're also found in patients with other rheumatic or connective tissue disorders.
  Anti-La/SS-B antibodies are found in approximately 40% of Sjögren's syndrome patients, especially those who have the primary form.

• Other immunological tests include an erythrocyte sedimentation rate, rheumatoid factor, anti-nuclear antibody and immunoglobulin test.

• As mentioned earlier, measuring saliva production and examining the salivary glands with or without a lip biopsy of the minor salivary glands (an oral surgeon or an ear/nose/throat specialist should perform this procedure) can determine the presence of lymphocytes in these glands and aid you in making the decisive diagnosis of Sjögren's syndrome.

Managing Sjögren's patients

Early diagnosis and intervention can affect the course of the disease. Treatment depends on symptoms and severity. Proper management is needed for your patients to enjoy a comfortable lifestyle.

"Management of patients with Sjögren's is complex. Symptoms requiring the services of many specialists can present in a single patient," notes Dr. Arthur I. Grayzel, president of the Sjögren's Syndrome Foundation, at the recent National Institutes of Health (NIH) program, "Sjögren's Syndrome: Treating the Whole Patient."

Here are some approaches to therapy for this problem:

• Over-the-counter (OTC) artificial tears and saliva substitutes can ease dryness symptoms of the eye and mouth. If your patients use artificial tears 4 or more times a day, recommend preservative-free eye drops. Preservative-free eye ointments at bedtime provide overnight relief from dry eye.

• Consider punctal occlusion if tear supplements don't help.

• For patients suffering from the thick mucous strands that often accompany KCS, consider acetylcysteine drops. Explain that ocular application of this compound isn't FDA approved.
  Commercially available acetylcysteine preparations (Mucomyst, Mucosil) are approved for use as pulmonary aerosols only and come in 10% and 20% solutions. The solutions often sting and are rarely tolerated for long periods; they also have offensive odors. Compounding pharmacists can make a pH-balanced solution that's diluted for better eye tolerance. The International Academy of Compounding Pharmacists maintains a list of compounding pharmacists. You can visit their Web site at www.iacprx.org.

• Successful treatment has been reported using low-dose oral cyclosporine (1 mg/kg/day), a systemic immunosuppressant. Topical cyclosporine A 0.05% (Restasis) shows promise for treatment of inflammatory corneal conditions and may reduce the lacrimal gland inflammation in Sjögren's syndrome. It's been used by veterinary ophthalmologists since 1989 to treat ocular surface inflammatory disease and KCS in animals.

• Recent studies by Sullivan and others at the Schepens Eye Research Institute suggest that androgen deficiency may promote progression of Sjögren's syndrome. Topical androgen may serve as a safe and effective therapy for dry eye in Sjögren's.

• Patients should wear protective eyewear to avoid sun and wind exposure. Moisture chamber eyeglasses may prove effective for alleviating dry eye symptoms. These glasses create a chamber that provides a humid environment behind the eyeglass lens and in front of the eye surface to prevent tear evaporation. Moisture chamber panels are available from EagleVision. For more information, visit their Web site at www.Eaglevis.com.
  Other measures to improve moisture include: use of a humidifier or vaporizer to maintain air moisture indoors; avoidance of drafts from air conditioners, fans and radiators; and use of moisturizing lotions to treat dry skin and saline sprays for dry nose.

• Sjögren's patients need to brush and floss their teeth regularly and restrict sugar intake to prevent tooth decay. Have them chew sugarless gum to stimulate saliva production, and drink water frequently to keep the mouth moist. Patients should avoid caffeinated and alcoholic beverages because they increase oral dryness.

Medications for Sjögren's

Prescription medications designed to stimulate saliva and mucus production are available. Pilocarpine tablets (Salagen 5 mg) can increase salivary flow for 1 to 2 hours after absorption. Patients with uncontrolled asthma, gastrointestinal ulcer, acute iritis or narrow-angle glaucoma shouldn't use this drug. Nor should those who are pregnant. It also may not be suitable for patients with unstable cardiovascular disease. The patient's physician can titrate individual doses, usually in the range of 5 mg t.i.d. to 10 mg q.i.d.

Another saliva-stimulant drug is cevimeline (Evoxac 30 mg). You can find more information on Daiichi Pharmaceutical's Web site at www.daiichius.com.

Systemic iodides, prescribed as potassium iodide, promote nasal and throat secretions. They're usually safe. Side effects include iodine allergy and stomach upset. Guaifenesin, the main ingredient in most OTC expectorants, increases respiratory tract fluid and helps loosen phlegm and mucus. It's available in a more concentrated form by prescription.

Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and immunosuppressant drugs are also often used.

"We treat the most troublesome areas symptomatically," said Dr. Carsons. "We give the most attention to the area of most clinical activity. "Fortunately, the joint pain and arthritis that occur with Sjögren's are usually mild. We often use NSAIDs like ibuprofen or aspirin. When fatigue or low-grade fever is reported, we suggest hydroxychloroquine (Plaquenil) that has a 50-year track record with rheumatoid arthritis and lupus, and is now being used for Sjögren's."

Reach out

The Sjögren's Syndrome Foundation publishes The New Sjögren's Syndrome Handbook and a newsletter. They can advise your patients of support groups. Patients who call 1-800-475-6473 will receive a free information package.

You may contact or refer patients to the Sjögren's Syndrome Foundation, 366 North Broadway, Ste. PH-W2, Jericho, NY 11753. Call (516) 933-6365, or visit www.sjogrens.org. I found them to be extremely helpful and owe them a debt of gratitude for their help in the preparation of this article.

You're in a unique position to detect and manage Sjögren's syndrome. Know what to ask and what tests to perform. Your patients depend on you.

References available upon request.

Dr. Bowling practices in northwest Georgia. He's a member of Optometric Management's editorial board, a multiple recipient of the AOA Optometric Recognition Award and is a clinical examiner with the National Board of Examiners in Optometry.