2. Sjögren’s Syndrome :Dental Role in Providing Relief

James J. Sciubba, DMD, PhD and Erwin D. Mandel, DDS

Introduction

Sjögren’s syndrome is an autoimmune disease in which sensitized lymphocytes selectively seek, infiltrate and destroy exocrine glandular tissue, including salivary glands. Lacrimal glands are also affected and, as a result, the sicca complex is clinically characterized by depressed levels of tear and saliva production.

Sjögren’s syndrome is estimated to affect more than one million people in the United States. It is seen predominantly in middle-aged and elderly women, with females being affected 10 times more frequently than males.

Clinical Findings

Primary Sjögren’s syndrome consists of dry eyes and dry mouth. These same symptoms are seen in secondary Sjögren’s syndrome, along with an associated extraglandular connective tissue disease, such as rheumatoid arthritis or systemic lupus erythematosus. To establish the diagnosis of primary Sjögren’s, it is essential to perform a lip biopsy to confirm that immune cells within the minor salivary gland tissue are causing the dry mouth. Additionally, it is necessary to demonstrate antinuclear antibodies in blood to specific tissue antigens (Ro/SS-A or La/SS-B).

To establish the diagnosis of secondary Sjögren’s syndrome, definite dry eyes and dry mouth and/or a lip biopsy must be obtained in addition to serologic evidence of an accompanying connective tissue disease, usually rheumatoid arthritis. From a serological perspective, primary Sjögren’s syndrome patients will often have a particular type of gene known as HLA-B8-DR3, while secondary Sjögren’s syndrome will often show the genetic subtype of HLA-DR4 if the patient has rheumatoid arthritis.

It is thought that genetic factors render an individual susceptible for triggering of the autoimmune reaction, which to date remains poorly understood. Some experts believe that these genetic factors, plus infectious agents, may be responsible for generating the autoimmune attack on all exocrine glands in a manner similar to that noted in diabetes or thyroiditis. In these latter cases, glandular tissue is destroyed by activated lymphocytes mentioned above in the presence of auto-antibodies. Candidates for infectious agents have been mentioned in the past. They include the Epstein-Barr virus; and more recently, a retroviral etiology has been suggested.

Differential Diagnosis

Since the most common cause of xerostomia is medication, the differential diagnosis must include, in addition to Sjögren’s syndrome, use of certain drugs or medications. These include a long list of anticholinergics, antidepressants, anorectics, antipsychotics, sedatives, antihistamines, antihypertensive agents and diuretics. The clinician must carefully review current use of prescription and non-prescription medications before proceeding further. Patients who have received therapeutic radiation to the head and neck, including the major salivary glands, for diseases such as lymphoma or carcinoma are certain to have variable levels of xerostomia.

Organic diseases as well as autoimmune ones should be considered. These include the HIV complex, diabetes mellitus, hypertension, cystic fibrosis and dehyrdration secondary to impaired water intake. Diarrhea, renal disease and osmotic diuresis should also be included in the differential diagnosis. Psychogenic factors, in particular depression, can produce xerostomia as can decreased mastication due to limited intake of liquids or soft foods. (Table 1).

Table 1. Differential Diagnosis of Xerostomia

medications irradiation to head and neck region depression organic diseases (autoimmune diabetes, hypertension, dehydration) soft diet and decreased mastication

Diagnosis of Sjögren’s syndrome involves clinical tests and development of criteria for diagnosis. (Table 2). Several attempts to better define such components have been made over the years. Xerostomia is a likely clinical diagnosis if patients present with signs or symptoms over the dorsum of the tongue, such as atrophy or cobblestone surface changes. If such changes are present along with salivary gland enlargement, a reduction in salivary flow greater than 50 percent, and positive or so-called abnormal findings in salivary gland biopsy material, the diagnosis can be safely stated. The addition of reduced lacrimal flow rate, as measured by a Schirmer tear test, and punctate or filamentary keratitis establishes the diagnosis.

While these criteria are rather objective, the diagnosis of Sjögren’s syndrome may be strongly suspected during the initial history and physical examination of the patient. Patients will often relate difficulty, if not an inability, to swallow a dry bolus of food, the so-called “cracker sign.” Patients will likewise complain of a sandy or gritty sensation of the eyes, often accompanied by burning. Further oral signs include burning of the oral mucosa in some patients, oral mucosal erythema, stickiness of the oral mucosa, parotid gland enlargement or induration (hardening of the tissues) and the presence of focal sialoadenitis (inflammation of a salivary gland) upon analysis of a minor salivary gland biopsy.

Table 2. Methods of Evaluating Salivary Status

sialometry sialography sialochemistry (99m Tc) imaging (ultrasound, CT, MRI) labial biopsy

In assessing salivary gland enlargement, in particular of the parotid glands, the clinician must determine if the swelling is unilateral or bilateral. If the former, the clinician should suspect potential salivary gland neoplasia or bacterial infection. When bilateral, lymphoma, granulomatous diseases such as sarcoidosis or tuberculosis, recurrent parotitis of childhood and sialadenosis, must be considered along with the benign lymphoepithelial lesion that usually accompanies Sjögren’s syndrome.

With sialadenosis, the clinician must rule out potential underlying factors, including diabetes mellitus, hepatic cirrhosis, anorexia/bulimia, hypolipoproteinemia and chronic pancreatitis.

Symptoms associated with xerostomia include difficulty with speech, inability to chew and swallow dry food, a burning or tingling sensation of the oral tissues, in particular the tongue and an increase in dental caries. Bacterial sialoadenitis is often a common sequela of advanced and chronic xerostomia. Patients will often have difficulty coping with prosthetic appliances. Reduction in self-cleansing can result in increased plaque retention with a resultant increase in the incidence of periodontal disease as well as rates of disease progression.

The fundamental nature of Sjögren’s syndrome and the accompanying xerostomia produce symptoms and signs centered exclusively on the diminution of saliva. The output of protective salivary constituents is altered significantly, thus setting the stage for alterations in the oral environment or ecology and the disease processes and breakdown that occur later. One such change in the microbial flora is colonization of the oral cavity by coliforms and Staphylococcus aureus. This shift appears to be common regardless of the etiology of xerostomia, that is, whether it is related to Sjögren’s syndrome, radiation therapy or medication-induced dryness. Other changes in the oral microflora include an increase in Streptococcus mutans and Candida albicans levels. This, in turn, is responsible for the heightened incidence of caries and candidiasis, respectively.

Clinical Considerations

The impact of chronic xerostomia on the patient and on the dental practitioner can be devastating. The patient must be educated relative to Sjögren’s syndrome, its general course and the fact that it is essentially incurable. At the same time, the practitioner should encourage the patient by indicating that the disease effects are manageable and with his/her cooperation the symptoms can be reduced and irreversible damage prevented.

An individual treatment plan must be devised for each patient to prevent new as well as recurrent dental caries. Daily fluoride mouth rinses are critical as is dietary modification–including discontinuing sugar-containing foods and beverages between meals–scrupulous daily oral hygiene, and routine and frequent dental examinations and treatment.

In patients with severe xerostomia, it is often necessary to use custom-made, soft acrylic trays or stents in conjunction with therapeutic-strength fluoride gels in an effort to help prevent rampant caries. Additionally, daily use of remineralizing solutions have proven helpful in that the earliest phases of tooth destruction can be altered and in many cases reversed, provided the carious lesion is in an incipient phase where sufficient enamel matrix may remain for remineralization to occur.

The presence of oral candidiasis is often under appreciated and unfortunately quite problematic in approximately one-third of patients with Sjögren’s syndrome. Atrophic or erythematosus candidiasis will often have associated burning symptomatology with predisposition to ulceration. Less common, but by no means unusual, is pseudomembranous candidiasis, or so-called thrush. With thrush, curd-like aggregates of fungal colonies may be widely dispersed over the nonkeratonized mucosa and may be easily dislodged from the surface with gentle pressure.

Management of candidiasis involves the use of topically effective anti-fungal medications, which are generally sufficient. In more resistant or difficult circumstances, systemic anti-fungal drugs taken orally, such as ketoconazole and, more, recently, fluconazole, may be indicated. In individuals wearing partial or complete dentures, scrupulous hygiene and removal at bedtime, coupled with anti-fungal medications, are usually effective in controlling or eliminating fungal infection.

Salivary substitutes are currently available commercially and without prescriptions. Such substitutes fail to uniformly and completely suffice for natural saliva, yet they appear to be more effective than plain water and can provide relief for some patients. More recently, gel-based preparations have been introduced as well as salivary substitutes containing glycoproteins. These tend to more closely mimic natural saliva. Patients must be cautioned regarding chronic use of citric acid-containing drops. These could prove harmful in a short period of time in that tooth demineralization in the presence of relative dryness may quickly result.

Salivary stimulation by gustatory and/or masticatory means is the more common method for encouraging salivary flow. Use of sugarless chewing gum5 and sugarless hard candies often suffices for management of mild-to-moderate levels of xerostomia. Pharmacological intervention using pilocarpine can be effective in increasing salivary production is some patients.6 A single dose of pilocarpine can often produce approximately one to two hours of improved salivary flow in individuals with some level of residual salivary function. Side effects, however, must be monitored. These include sweating, gastrointestinal discomfort and cardiovascular complications in individuals with hypertension.

Finally, a recently developed electrical stimulation device claims to produce improved salivary function in individuals with xerostomia. While results have not been uniform, this device clearly would require functional residual salivary tissue in order to be effective. A recent report7 underscores lack of sufficient data relative to evaluation of long-term clinical effectiveness of this modality of salivary stimulation and, equally importantly, to identify those who would benefit from this approach.

Conclusions

While the causes for xerostomia are multiple, individuals with Sjögren’s syndrome tend to present with consistent and long-term xerostomia, which carries with it significant dental and oral complications. Both hard tissues and soft tissues can be affected with increase in the rates of caries and periodontal disease as well as oral mucosal discomfort and other factors that can severely affect quality of life. The dentist must be aware of this particular disease, its oral manifestations and their management.

References

1. Arthritis Medical Information Series: Sjögren’s Syndrome. Atlanta:Arthritis Foundation, 1988.
2. Moutsopoulos, HM; Mann, DL; Johnson, AH; Chuset, TM. Genetic differences between primary and secondary sicca syndrome. N. England J. Med. 301 :761-763, 1979.
3. Garry, RF; Fermin, CD; Hart, DJ, et al. Detection of a human intracisternal A-type retroviral particle antigenetically related to HIV. Science 250:1127-11129. 1990.
4. Sreebny, LK. Salivary flow in health and disease. Compend. Contin. Edu. Dent., Suppl. 13, S461-S469, 1989.
5. Odulosa, F. Chewing gum as an aid in treatment of hyposalivation. NYS Dent. J.57:28-31, 1991.
6. Fox, P; Atkinson, JC; Macynski, AA; Wolff, A., et al. Pilocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia). Arch. Omt. 151:1149-1152, 1991.
7. Salivary Electro stimulation in Sjögren’s Syndrome, Agency for Health Care Policy and Research, Report No. 8, 1991, DHHS Publication No. AHCPR 91-0009.

Source: New York State Dental Journal, August-Sept. 1992.

Reprinted with permission.