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Treatment of SS is complicated by its unique multiorgan involvement. Timely organ-specific treatment can effectively increase patient comfort and reduce potential damage to the corneas and teeth. Systemic complications of SS are secondary to autoimmune processes and potentially life-threatening, and are discussed below.

Ocular management of KCS has three goals: (i) replacing the aqueous tear film and restoring normal tear function through the use of preservative-free artificial tears; (ii) improving retention of the patient's diminished tear volume by closing lacrimal puncta, either temporarily or permanently; and (iii) treating various ocular complications that can lead to scarring of the cornea, such as persistent epithelial erosions, exposure keratitis, corneal ulceration, and chronic staphylococcus infection of the lid margins.

There are many forms of artificial tears that can be used for tear replacement, but those in multi-dose containers should be avoided. Multi-dose bottles contain preservatives to which many patients develop hypersensitivity reactions that may eventually lead to conjunctival scarring and a further decrease in tear production. Preservative-free single-unit-dose eye drops such as Refresh®, Cellufresh®, and Celluvics® are the most effective artificial tears, and do not cause chronic ocular irritation or damage to the cornea and conjunctiva. Artificial tears in multi-dose containers that claim to be preservative-free because the preservative is ephemeral can nevertheless cause irritation because of residual irritants, and should be avoided. Topical steroid preparations should not be used routinely in patients with KCS. If they are required in cases where inflammation is severe, they should be used judiciously with frequent careful follow-up examinations by an ophthalmologist. Commercially available topical preparations of 0.05% cyclosporine (Restasis®) improve symptoms in some patients with mild KCS, but in general they have very little effect on SS patients with severe KCS. Cyclosporine in 1% or 2% concentrations may prove to be more effective. Alternatives to commercially available preservative-free artificial tears include 1.25% gum cellulose drops, low molecular weight dextran, hyaluronic acid, fibronectin, and autologous human serum albumin.

When punctal occlusion does not lead to marked improvement of ocular symptoms, many patients find the use of moisture chamber glasses helpful. Wearing moisture chambers, soft rubber swim goggles, or saran wrap over the eyes while sleeping can increase ocular comfort for a few hours during the day. Environmental changes such as humidifying the bedroom can also be helpful. In extreme cases, a temporary tarsorrhaphy can be preformed to prevent corneal thinning, melting, and perforation while the underlying problem, whether it be infection or exposure, can be effectively addressed.

Treatment of the salivary and oral component of SS has four goals: (i) ongoing dental caries prevention through patient education about diet, oral hygiene, and the role of fluoride supplements; professionally applied and patient applied topical fluoride preparations; and dental restoration with procedures and materials appropriate to an oral environment of chronic salivary hypofunction; (ii) salivary flow stimulation with systemically administered drugs, such as pilocarpine or cevimeline, and physiological stimulation using sugar-free lozenges or gum; (iii) recognition of chronic erythematous candidiasis, which occurs in about one-third of SS patients, and its treatment with appropriate antifungal drugs which greatly reduce oral symptoms, even with continuing salivary hypofunction; and (iv) selective use of saliva substitutes, which remain in the mouth for a relatively short time and do not replace the functions of normal saliva, but can be helpful for patients with fairly severe chronic hyposalivation (7).

Topical fluoride application is critical for caries prevention in this susceptible population. Typically, the patient is stratified into a low, medium, or high risk caries group, and the use of the following types of fluoride, either alone or in combination, is considered: professionally-applied high-concentration fluoride solutions (e.g., 1.23% fluoride in acidulated phosphate fluoride gel for four minutes, four times per year; or a 2.26% fluoride varnish applied directly to the teeth, four times per year); patient-applied sodium fluoride gel (0.5% fluoride) in a custom-fitted tray for five minutes daily (to supplement professionally-applied fluoride); or a daily rinse with a 0.05% sodium fluoride, which is another useful addition to professionally-applied fluorides. Neutral sodium fluoride preparations are generally preferred to stannous fluoride preparations because patients tolerate them better. Chlorhexidine rinses may be used to control the quantity of mutans streptococci in the flora. This can be in the form of a patient-applied 0.12% chlorhexidine gluconate rinse, one minute daily for two weeks.

All currently available "oral" topical antifungal drugs contain substantial amounts of sucrose or glucose (i.e., brands of clotrimazole oral troches, nystatin oral pastilles, and nystatin oral suspension), which creates significant risk for supporting dental caries development when used as directed. Systemic antifungals may not be fully effective in those with severe salivary dysfunction, as the medication is delivered to the oral cavity through saliva. Therefore, the best topical antifungal drug to use with patients at high risk for dental caries is nystatin vaginal tablets. These do contain lactose, which is a potentially cariogenic carbohydrate, but much less so than either sucrose or glucose. They must be dissolved slowly in the mouth for 15 to 20 minutes, two or three times per day. Such patients usually must take frequent sips of water to allow the tablet to dissolve in that time. The treatment end-point for erythematous candidiasis should be resolution of all the mucosal erythema, return of filiform papillae to the dorsal tongue, and resolution of associated oral symptoms (i.e., burning sensation). Dentures will also need to be treated for fungus to decrease the risk of reinfection.

Organ-specific manifestations that require treatment are diverse and can be managed by a series of medical specialists (2,5,6). Those conditions can include chronic low-grade problems such as myalgias, polyarthralgias, fatigue, and Raynaud's phenomenon, or organ-specific diseases such as chronic interstitial lung disease, atrophic gastritis, peripheral neuropathies, primary biliary cirrhosis, and renal tubular acidosis, or hematological diseases such as nonthrombocytopenic purpura, leukopenia, and hyper-gammaglobulinemia, or non-Hodgkin's lymphoma. Systemic therapy for SS is currently limited to a few classes of drugs. Cholinergic agonists (i.e., pilocarpine, cevimeline) can be prescribed to stimulate salivary and lacrimal secretion. Vasculitic skin lesions or visceral involvement is usually treated with a corticosteroid alone or in combination with methotrexate, cyclphosphamide, or chlorambucil. Arthritis is usually managed, depending on the severity, with nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxylcholor-oquine, or methotrexate. TNF inhibitors (i.e., etanercept, infliximab) have not been effective for SS in clinical trials. Long-term immunosuppressive therapy should be used with caution in this population with a chronic, nonfatal disease process. A monoclonal antibody, Rituximab, is available for treatment of CD20+ B-cell non-Hodgkin's lymphoma.

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