Approach Considerations
No curative agents for Sjögren syndrome exist. The treatment of the disorder is essentially symptomatic. [78]
Skin and vaginal dryness
Patients should use skin creams, such as Eucerin, or skin lotions, such as Lubriderm, to help with dry skin. Vaginal lubricants, such as Replens, can be used for vaginal dryness. Vaginal estrogen creams can be considered in postmenopausal women. Watch for and treat vaginal yeast infections.
Arthralgias and arthritis
Acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) can be taken for arthralgias. Consider hydroxychloroquine if NSAIDs are not sufficient for the synovitis occasionally associated with primary Sjögren syndrome. However, hydroxychloroquine does not relieve sicca symptoms. Patients with RA associated with Sjögren syndrome likely require other disease-modifying agents.
Additional treatment considerations
In patients with major organ involvement, such as lymphocytic interstitial lung disease, consider therapy with steroids and immunosuppressive agents, such as cyclophosphamide.
While cyclophosphamide and similar agents may be helpful for treating serious manifestations of Sjögren syndrome or disorders associated with Sjögren syndrome, clinicians should understand that these agents are also associated with the development of lymphomas.
Long-term anticoagulation may be needed in patients with vascular thrombosis related to antiphospholipid antibody syndrome.
In a small group of patients with primary Sjögren syndrome, mycophenolate sodium reduced subjective, but not objective, ocular dryness and significantly reduced hypergammaglobulinemia and RF. [79]
Among the biologic therapies, the greatest experience in primary Sjögren syndrome is with rituximab, an anti-CD20 (which is expressed on B-cell precursors) monoclonal antibody. Anti-B–cell strategies, particularly rituximab, have a promising effect in the treatment of patients with severe extraglandular manifestations of Sjögren syndrome.
Reports on the use of rituximab in patients with primary Sjögren syndrome have emerged in the literature. [80, 81, 82] In a double-blind, randomized, placebo-controlled trial, Meijer et al found that rituximab significantly improved saliva flow rate, lacrimal gland function, and other variables in patients with primary Sjögren syndrome. [83]
In an open-label clinical trial, modest improvements were noted in patient-reported symptoms of fatigue and oral dryness. However, no significant improvement in the objective measures of lacrimal and salivary gland function was noted, despite effective depletion of blood B cells. [84] In a randomized, placebo-controlled, parallel-group study of 120 patients with primary Sjögren syndrome, treatment with rituximab did not alleviate disease activity or symptoms at week 24, although it did alleviate some symptoms at weeks 6 and 16. [85]
Rituximab appears promising in the treatment of vasculitis and intravenous immunoglobulin (IVIG)–dependent ataxic neuropathy. [86, 87] Results from the AIR registry (French) indicated that rituximab appears to be effective in cryoglobulinemia or vasculitis-related peripheral nervous system involvement in primary Sjögren syndrome. [88]
In a prospective study of 78 patients with primary Sjögren syndrome treated with rituximab, significant improvement in extraglandular manifestations was reported, as measured by EULAR [European League Against Rheumatism] Sjögren Syndrome Disease Activity Index (ESSDAI) (disease activity score) and overall good tolerance reported. [89] Several smaller studies of rituximab revealed improvement of arthralgias, regression of parotid gland swelling, [90] and improvement of immune-related thrombocytopenia. [91]
Of the TNF inhibitors, both etanercept and infliximab have failed to demonstrate significant benefit in Sjögren syndrome.
Combination therapy with leflunomide and hydroxychloroquine resulted in a significant decrease in ESSDAI scores and caused no serious adverse events, in a small phase 2a randomized clinical trial from the Netherlands. At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group (n=21), compared with the placebo group (n=7), was –4.35 points after adjustment for baseline values.
Fewer data are available with regard to the role of anti-CD22, anti-BAFF, anti-IL-1, type 1 interferon, and anti-T–cell agents in treatment of primary Sjögren syndrome, with further investigations ongoing. The overall paucity of evidence in therapeutic studies in primary Sjögren syndrome suggests that much larger trials of the most promising therapies are necessary. The investigators concluded that further evaluation of leflunomide–hydroxychloroquine combination therapy in larger clinical trials is warranted. [92, 93]
Emergency department care
The diagnosis of Sjögren syndrome can be made from the ED if the index of suspicion is high. Patients may present with mild symptoms (eg, eye grittiness, eye dryness or discomfort, dry mouth, recurrent caries). Bilateral parotid gland swelling is also a common presentation.
Patients with known Sjögren syndrome should not be taken lightly for their complaint of dry eyes or dry mouth, as these chronic problems can be very distressing and obtrusive.
Inpatient care
Give attention to artificial lubricants and humidified oxygen for intubated and/or sedated patients with Sjögren syndrome.
Outpatient care
Encourage patients with Sjögren syndrome to be active. In addition, patients should be encouraged to avoid exacerbation of dryness symptoms (eg, through smoking or exposure to low-humidity environments). All patients with Sjögren syndrome should be monitored by an ophthalmologist and dentist, in addition to their rheumatologist. Certain patients may be candidates for punctal occlusion, which is usually performed by an ophthalmologist.
Monitoring
Most patients with Sjögren syndrome can be monitored at follow-up visits every 3 months and, if the patient is stable, up to every 6 months. Patients with active problems or in whom an emerging associated illness is a concern can be seen as often as monthly.
Surgical Therapy
Occlusion of the lacrimal puncta can be corrected surgically. Electrocautery and other techniques can be used for permanent punctal occlusion.
During surgery, the anesthesiologist should administer as little anticholinergic medication as possible and use humidified oxygen to help avoid inspissation of pulmonary secretions. Good postoperative respiratory therapy should also be provided. Patients are at higher risk for corneal abrasions, so ocular lubricants should be considered.
Biopsies that may be performed in association with Sjögren syndrome include the following:
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Minor salivary gland biopsy - For diagnostic purposes
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Parotid gland biopsy - If malignancy is suggested
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Biopsy of an enlarged lymph node - To help rule out pseudolymphoma or lymphoma
Consultations
Sjögren syndrome and its associated disorders necessitate a total patient perspective that is often best provided by an internist. A rheumatologist with specific training and experience in Sjögren syndrome and its associated disorders is also essential to the management of the condition. In addition, good oral prophylaxis and therapy are necessary.
Involve ophthalmologists early in the care of patients, for rose bengal and fluorescein staining to help to establish the diagnosis and for assessment of the degree of eye damage.
Consultation with an otolaryngologist may be needed early to perform a minor or major salivary gland biopsy if this is deemed necessary to establish a diagnosis. The specialist may also need to perform a parotid biopsy if malignant transformation is suggested.
Depending on the problems, patients with Sjögren syndrome may need to be seen by other specialists, including the following:
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Nephrologist - To help manage renal tubular acidosis
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Pulmonologist - To help manage interstitial lung disease
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Hematologist/oncologist - If pseudolymphoma or lymphoma develops
Dry Eyes
The treatment of dry eyes depends on the severity of the dryness, which is best determined by an ophthalmologist and is graded according to the following [94, 95, 96, 97, 98, 99] :
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Degree of symptoms
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Conjunctival injection and staining
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Corneal damage
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Tear quality
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Lid involvement
New therapeutic strategies designed to facilitate AQP5 trafficking to the apical plasma membrane may prove useful in the management of dry eyes in Sjögren syndrome. In addition, data on novel secretagogues and androgen therapies for dry eyes are promising. [86]
A consensus clinical guideline for the management of dry eyes associated with Sjögren syndrome recommends the following [100] :
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Patient evaluation should include symptoms of both discomfort and visual disturbance along with evaluation of the relative contribution of aqueous production deficiency and evaporative loss of tear volume
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Objective parameters of tear film stability, tear osmolarity, degree of lid margin disease, and ocular surface damage should be used to stage disease severity and assist in guiding treatment
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Successful management requires patient education on the nature of the problem, aggravating factors, and treatment goals
Treatment options are used according to the severity and character of dry eye disease and include the following [100] :
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Tear supplementation and stabilization
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Control of inflammation of the lacrimal glands and ocular surface
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Possible stimulation of tear production
Level 1 - Mild symptoms, no corneal signs
Artificial tears should be applied liberally. Patients may need to apply artificial tears more often if they enter a low-humidity environment (ie, air conditioning, airplanes). Artificial tears with hydroxymethylcellulose or dextran are more viscous and can last longer before reapplication is needed. Encourage patients to try various preparations to determine what works best for them.
If artificial tears burn when they are instilled, the preservative in the artificial tears is likely irritating the eye. If artificial tears are used more often than every 4 hours, patients should use a preservative-free preparation to avoid eye irritation from the preservatives.
The use of humidifiers may help. If the patient is living in an area with hard water, he or she should use distilled water. Patients should avoid medications with anticholinergic and antihistamine effects.
Level 2 - Moderate or severe symptoms with tear film signs or visual signs, or mild corneal/conjunctival staining
Patients should use unpreserved tears or gels or nighttime ointments. Patients who wake up in the morning with severe matting in the eyes should use a more viscous preparation (eg, Lacri-Lube) at night. While the more viscous preparations can be applied less often, they can make patients' vision filmy. Therefore, they are best used at night. The more viscous preparations occasionally lead to blepharitis, which can exacerbate sicca symptoms.
The following agents may also be indicated:
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Topical steroids
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Secretagogues
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Cyclosporine A [101]
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Nutritional supplements
Level 3 - Severe symptoms with marked corneal changes or filamentary keratitis
The following treatments may be indicated:
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Tetracyclines
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Autologous serum tears
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Temporary plugging of the lacrimal puncta to increase the amount of tears that remain in the eyes
Level 4 - Extremely severe symptoms with altered lifestyle, or severe corneal staining, erosions, or conjunctival scarring
The following therapies may be indicated:
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Systemic anti-inflammatory therapy, including acetylcysteine
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Topical vitamin A
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Electrocautery and other techniques for permanent punctal occlusion
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Glasses fitted with moisture shields to decrease evaporation
Dry Mouth
Patients with dry mouth can liberally drink sips of water and take bottled water with them on trips. They can also place a glass of water at their bedside for nighttime use, as needed. [102] Sugar-free lemon drops can also be used as needed to stimulate salivary secretion. Artificial saliva can be used as needed, although patient tolerance varies. Preparations include Salivart, Saliment, Saliva Substitute, MouthKote, and Xero-Lube. Patients should avoid medications with anticholinergic and antihistamine effects.
The use of humidifiers may help. Distilled water is best in patients living in an area with hard water.
Patients should be seen regularly by a dentist, who may advise fluoride treatments. Toothpaste without detergents can reduce mouth irritation in patients with Sjögren syndrome. Brands include Biotene toothpaste, Biotene mouth rinse, Dental Care toothpaste, and Oral Balance gel.
Watch for oral candidiasis and angular cheilitis and treat them with topical antifungal agents, such as nystatin troches. Oral fluconazole may occasionally be needed. Patients also need to be sure to disinfect their dentures.
Sinusitis and sinus blockade should be treated because these problems may contribute to mouth breathing. Emphasize the use of isotonic sodium chloride solution nasal sprays to avoid antihistamine use.
Pilocarpine or cevimeline tablets are options. Some small studies suggest that interferon alfa may be a useful therapy in the future.
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Marked bilateral parotid gland enlargement in a patient with primary Sjögren syndrome. Sicca syndrome is a common clinical finding. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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Clinical photograph and photomicrograph of a 48-year-old man with Sjögren syndrome with a large left parotid mass. On biopsy, B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type was identified. Microscopic section of parotid biopsy, stained with immunoperoxidase for kappa light chains (brown-stained cells), showed monoclonal population of B cells, confirming the diagnosis. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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Photograph that demonstrates the Schirmer test, which is used to detect deficient tear production in patients with Sjögren syndrome. The filter paper strip is placed at the junction of the eyelid margins. After 5 minutes, 15 mm of paper should be moistened if tear production is normal, as shown here. Persons older than 40 years may moisten between 10 mm and 15 mm. Patients with Sjögren syndrome have less moistening. Sjögren syndrome is most common in patients with rheumatoid arthritis but may also occur without associated disease and in systemic lupus erythematosus, polyarteritis, systemic sclerosis, lymphoma, and sarcoidosis. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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Dryness of the mouth and tongue due to lack of salivary secretion is characteristic of xerostomia associated with Sjögren syndrome. Mouth dryness may produce a deep red tongue, as shown here, and dental caries are common. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
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Photomicrograph of a lip biopsy specimen showing two lymphocytic foci adjacent to normal-appearing mucinous acini typical of minor salivary gland abnormalities in Sjögren syndrome. (C) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.
