Sjögren's Syndrome

     Sjögren's syndrome (SS) is a chronic inflammatory disorder characterized by diminished lacrimal and salivary gland function. SS occurs in a primary form not associated with other diseases and in a secondary form that complicates other rheumatic conditions. The most common disease associated with secondary SS is rheumatoid arthritis. In primary or secondary SS, decreased exocrine gland function leads to the "sicca complex", a combination of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). In addition, a wide variety of other disease manifestations can occur in SS. The clinical manifestations of SS are divided into the exocrine gland features and the extraglandular disease features.
     Keratoconjunctivitis sicca (KCS) is the preferred term (over "xerophthalmia") when referring to the ocular dryness associated with SS. The ocular symptoms of dry eyes are irritation, grittiness, and a foreign body sensation.
     Xerostomia — The oral dryness of SS leads to difficulty swallowing dry food such as crackers without drinking liquids. Oral dryness is associated with an increased rate of dental caries and periodontal complications and often a decrease in the sense of taste and a change in oral flora, including an increase in oral candidiasis.
     The KCS and xerostomia of SS are caused by immune-mediated inflammation directed against the exocrine glands of the eye and mouth. The histologic features include extensive lymphocytic infiltration, accompanied by glandular and ductal atrophy). This lymphocytic infiltration is organized in germinal center-like structures. KCS usually presents insidiously over a period of several years. The symptoms vary and are often worse in the evening. Affected patients may complain of "gritty" or "sandy" feeling in their eyes rather than describing "dryness. Other symptoms include irritation, itching, photophobia, and the accumulation of thick, rope-like strands (mucus filaments) at the inner side of the eye. Mucus filaments are particularly present upon awakening. Complications of KCS include corneal ulceration and infection of the eyelids.
     Physical examination may reveal one or more of the following findings: Punctate conjunctival and corneal damage, as detected by Rose Bengal or fluorescein. Evidence of reduced tear production, as detected by a Schirmer test. The effects of SS on the oral cavity result from chronic salivary hypofunction. Dry mouth is a common symptom, particularly in the elderly. Confirmation that the symptoms of dryness are due to SS often requires a salivary gland biopsy. This procedure is performed routinely on an outpatient basis. However, salivary gland biopsy is not necessary in all patients. Primary SS is often associated with autoantibodies directed against either the Ro/SSA or La/SSB antigens. The combination of clinical features consistent with SS and the finding of anti-Ro/SSA or anti-La/SSB antibodies generally precludes the need for salivary gland biopsy. Patients may complain directly of oral dryness or of complications such as dysphagia, adherence of food to buccal surfaces, problems with dentures, changes in taste, or an inability to eat dry food or to speak continuously for long periods.
     Salivary gland enlargement occurs in 30 to 50 percent of patients with SS at some point during the course of the disease. The glands are usually firm, diffuse, and nontender. These changes are most obvious in the parotid glands, but the submandibular glands may be affected to the same degree. Salivary gland enlargement may be either chronic or episodic.
     Involvement of exocrine glands in the upper airways leads to symptoms related to the nose, sinuses, and posterior pharynx in 50 to 70 percent of patients with SS. Such patients can have recurrent non-allergic rhinitis and sinusitis. The most common symptom of laryngeal, tracheal, and bronchial involvement is a dry cough, which may be persistent and irritating. If the patient does not have other features of SS, the diagnosis may be missed and the patient treated incorrectly for asthma or bronchitis. Only 20 percent of affected patients have abnormalities that can be identified by rhinoscopy or indirect laryngoscopy.
     Treatment of dry mouth aims to alleviate symptoms and prevent complications such as dental caries, gum disease, halitosis, salivary gland calculi. and dysphagia. Two major components of this regimen are stimulation of existing salivary flow and replacement of salivary secretions. Stimulation of existing salivary flow — Simply sucking on sugarless candies or dried fruit slices such as peaches or nectarines can stimulate flow in many patients. Citrus flavored sugarless tablets are available. These tablets may also contain malic acid, normally found in fruits such as apples or pears, which stimulates salivary flow. Use of maltose lozenges may reduce symptoms of oral dryness. Sugar-free chewing gums, containing various sweeteners such as aspartame, saccharin, and sorbitol can also be helpful. Care must always be taken not to increase the risk of dental caries.
     Pilocarpine — Pilocarpine (Salagen®), a muscarinic agonist that stimulates predominantly muscarinic M3 receptors, used at doses of 5 mg three or four times daily, can significantly increase aqueous secretions in patients with residual salivary gland function. Unfortunately, side effects (sweating, abdominal pain, flushing, increased urination) may limit its use. In addition to effects upon xerostomia, pilocarpine may improve symptoms of ocular dryness, although without any objective change in tear production.
     Cevimeline (Evoxac®) is a derivative of acetylcholine with a higher affinity for muscarinic M1 and M3 receptors on the lacrimal and salivary epithelium than for receptors on heart tissue. Doses of 30 or 60 mg three times daily alleviate the symptoms of dry mouth, dry eyes, and stimulate salivary flow; the 30 mg dose is nearly as effective as the higher dose and is better tolerated. Major side effects of cevimeline include excessive sweating, nausea, rhinitis, diarrhea, and visual disturbances. It is contraindicated in patients with asthma, narrow-angle glaucoma, or iritis.
     Replacement of oral secretions — Replacement of oral secretions is most simply accomplished by frequent sips of water. The water does not have to be swallowed, but can be rinsed around the mouth and expectorated. Although water provides temporary moisture, it does not provide the lubricating properties that are characteristic of the mucin/water mixtures that constitute normal saliva. A number of artificial saliva preparations that provide more viscosity/lubrication than water are available. These preparations contain hypromellose or methylcellulose, sometimes with animal mucins to reduce viscosity. There seems to be wide variation in individual preferences and, given the large number of products available, it is logical to encourage patients to try several different formulations.

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