Dr. Triantafyllopoulou is Senior Resident, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York. Dr. Triantafyllopoulou reports no commerical conflicts of interest.
Have you noticed that your mouth is often dry? Or that your eyes feel like they have sand in them? If so, you may be suffering from an autoimmune disorder that affects more people than rheumatoid arthritis and that often goes undetected.
The disorder, Sjogren's syndrome (SS), occurs in 1-3% of people, yet SS remains undiagnosed more than half of the time. Women are affected much more often than men (ratio of 9:1). Though the syndrome can appear at any age, Sjogren's occurs primarily among women in their thirties or forties.
It is important to establish a diagnosis of SS for a number of reasons because treatment can improve an unsuspecting patient's quality of life. And, for a small group of patients with the disorder, who may be at an increased risk for the lymphoma, a malignant cancer, early diagnosis is especially important.
Primary and Secondary SS
Doctors have classified SS into two types: primary (pSS) when it occurs alone and secondary (sSS) when it is accompanied by another autoimmune disorder such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or scleroderma.
Signs and Symptoms of SS
As shown in Table 1, manifestations can be thought of as:
- Glandular, which result from destruction of glands by an invasion of lymphocytes (white blood cells)
- Systemic, which are characterized by lymphocyte invasion of the skin, lungs, kidneys or peripheral nervous system.
Table 1.
Manifestations of Sjogren's Syndrome.
Glandular Manifestations
- Xerostomia (dry mouth)
- Parotid gland enlargement
- Xerophthalmia (dry eyes)
- Xerotrachea (dry trachea)
- Dyspareunia (painful sexual intercourse)
- Fatigue
- Raynaud's phenomenon, easy bruising (purpura), recurrent hives (urticaria)
- Arthralgias/arthritis
- Lung involvement
- Difficulty swallowing food
- Inflammation of the kidneys (interstitial nephritis)
- Peripheral neuropathy
- Lymphoma
Glandular Manifestations
Xerostomia(from the Greek words xeros=dry and stoma=mouth, to describe destruction of salivary glands resulting in dry mouth): along with dry eyes (xerophthalmia), the presence of dry mouth helps the doctor make the diagnosis (see Table 2). Patients with xerostomia may complain of dry mouth, frequent need to drink fluids, or may simply complain of an unpleasant taste, difficulty eating dry food, soreness of the mouth and throat, or difficulty using dentures.
On exam, the affected patient has little or no saliva in the floor of their mouth; in advanced disease, the surface of the tongue becomes red and lobulated, with partial or complete depapillation.
Normally, the salivary glands produce 1-1.5 L of saliva every day, which help fight bacteria, so that, in its absence, patients with SS are prone to develop dental carries and increased rate of oral bacterial infections with Streptococcus mutans and Lactobacillus. Furthermore, SS is the most common cause of acute bacterial infection of the salivary glands (sialadenitis). Acute bacterial sialadenitis produces a tender swelling of the salivary gland and, sometimes, other lymph node enlargement, fever and malaise.
Dry mouth, however, is not specific for SS and can be found in a number of other conditions as listed in Table 2.
Table 2.
Differential Diagnosis (D/D) of Sjogren's Syndrome.
| D/D of dry mouth | D/D of parotid gland enlargement | D/D of dry eyes |
|---|---|---|
|
Bilateral
|
|
Parotid gland enlargement:The parotid gland, a salivary gland, is located below and in front of each ear, and is often enlarged, occurring in 60% of patients with pSS. It may appear once in a while or as chronic persistent enlargement. Parotid gland enlargement may present on one side only (unilateral) but usually affects both parotid glands (bilateral).
Xerophthalmia(destruction of the lacrimal glands resulting in dry eyes): This is the second of the two subjective criteria for the diagnosis of SS. A broader term for this condition is "keratoconjunctivitis sicca," denoting the clinical findings that result from destruction of covering protective eye tissue whose function it is to bathe the eye.
Patients with xerophthalmia will complain of itching, burning and a sensation of gravel or sand in their eyes. They may also complain of redness of their eyes, photosensitivity, eye fatigue and a discharge from their eyes. These symptoms are made worse by dry climates and air-conditioned environments or with exposure to cigarette smoke. Untreated, xerophthalmia may be complicated by corneal ulceration, vascularization, opacification and, more rarely, corneal perforation.
Destruction of the exocrine glands that line the oropharynx (the back of the mouth behind the soft palate) and the windpipe (trachea) may result in hoarseness and a chronic dry cough. A patient's stomach may also produce less gastric acid (hypochlorhydria), while dryness of the vagina can cause painful sexual intercourse (dyspareunia), though fertility is not thought to be affected. More than half of SS patients also complain of dry skin.
The presence of any 4 out of 6 criteria is indicative of the diagnosis of pSS with a high degree of certainty (sensitivity of 97% and a specificity of 89%). If 3 out of the 4 objective criteria are present, then pSS can be diagnosed with a sensitivity of 84% and a specificity of 95%, even if the patient doesn't complain of dryness.
sSS is diagnosed when 1 of the 2 subjective and 2 of the 4 objective criteria are present in a patient with another well-defined connective tissue disease. These criteria and the studies that validated them stress the importance of objective blood tests for specific antibodies (Ro and La autoantibodies) and histopathology studies. Histopathology refers to the examination of minor salivary glands that are removed with a small (~1cm) incision of the skin (biopsy) overlying the lower lip. The size and number of white blood cells groupings that are adjacent to salivary ducts are counted. It is important to remember that other diseases such as sarcoidosis and AIDS (HIV sialadenitis) may look the same &8212; so it's extremely important that an experienced pathologist to interpret the biopsy and keep in mind the full clinical picture of the patient.
Revised Criteria for the Diagnosis of SS
In 2002, an American-European consensus group proposed revised diagnostic criteria (see Table 3).
Table 3.
Diagnostic Criteria for Sjogren's Syndrome.
Two Subjective Criteria:
Four Objective Criteria:
Exclusion Criteria:
- Ocular symptoms: persistent dry eyes (>3 months)
- Oral symptoms: persistent dry mouth
Four Objective Criteria:
- Signs of dry eyes: positive Shirmer's test or positive Rose Bengal score upon ophthalmologic evaluation
- Histopathology of lip biopsy: minor salivary glands with lymphocytic infiltrates
- Presence of either Ro or La autoantibodies in the serum
- Objective measurements of decreased salivary gland function (e.g., less saliva)
Exclusion Criteria:
- Hepatitis C infection
- AIDS
- Sarcoidosis
- Pre-existing lymphoma
- Past history of head and neck irradiation
- Graft vs. host disease
- Use of anti-cholinergic drugs
The presence of any 4 out of 6 criteria is indicative of the diagnosis of pSS with a high degree of certainty (sensitivity of 97% and a specificity of 89%). If 3 out of the 4 objective criteria are present, then pSS can be diagnosed with a sensitivity of 84% and a specificity of 95%, even if the patient doesn't complain of dryness.
sSS is diagnosed when 1 of the 2 subjective and 2 of the 4 objective criteria are present in a patient with another well-defined connective tissue disease. These criteria and the studies that validated them stress the importance of objective blood tests for specific antibodies (Ro and La autoantibodies) and histopathology studies. Histopathology refers to the examination of minor salivary glands that are removed with a small (~1cm) incision of the skin (biopsy) overlying the lower lip. The size and number of white blood cells groupings that are adjacent to salivary ducts are counted. It is important to remember that other diseases such as sarcoidosis and AIDS (HIV sialadenitis) may look the same &8212; so it's extremely important that an experienced pathologist to interpret the biopsy and keep in mind the full clinical picture of the patient.
Treatment
Treatment of glandular manifestations of the disorder is symptomatic. The goal is to attempt to reduce future complications and improve quality of life:
- Xerostomia is treated with drugs know as muscarinic agonists. Two are now available in the U.S.: pilocarpine hydrochloride, which is dosed as 5 mg tablets 4 times daily, and cevimeline hydrochloride, given as 30 or 60 mg tablets three times daily. Side effects may include excessive sweating (less often with cevimeline), nausea, inflammation of the nasal passages (rhinitis) and diarrhea. Frequent dental visits are advised to prevent and treat dental carries and oral infections. Patients with SS should avoid, if possible, tricyclic antidepressants, beta blockers and diuretics, since these may worsen their symptoms.
- Xerophthalmia is treated primarily with topical hydrophilic solutions to prevent complications such as corneal ulceration. Blocking the outflow ducts in the eyes, through the insertion of plugs, or permanent occlusion, through electrocautery, are also employed to preserve existing tears. Pilocarpine and cevimeline may also be used for xerophthalmia. Topical cyclosporine A has recently been reported as effective for xerophthalmia. Treatment of systemic manifestations is usually centered on non-aggressive symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or even low-dose corticosteroids or hydroxychloroquine for arthralgias. Long-term immunosuppression has not been shown to be of benefit and is hazardous, especially since the syndrome usually does not carry an increased mortality. Moderate doses of corticosteroids may be used in patients who have severe skin lesions or who have kidney disease.
Conclusions
SS is a common chronic autoimmune disorder that may present with numerous signs and symptoms. A diagnosis of the syndrome can be made if there is subjective evidence of eye or mouth dryness along with objective findings of reduced tear and/or saliva secretion, and, most importantly, positive Ro or La autoantibodies or positive minor salivary gland histopathology (from lip biopsy). In the majority of patients, their disease course is mild and treatment is mostly symptomatic.
