eMedicine Specialties > Ophthalmology > Connective Tissue Disorders
Sjogren Syndrome: Treatment & Medication
Updated: Feb 19, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- After diagnosing Sjögren syndrome, treatment is aimed at providing symptomatic relief by lubricating the ocular surface. Artificial tears and lubricating ointments form the mainstay of treatment. A large variety of preparations is available, but none is as efficacious as the patient's own tears. Topical autologous serum eye drops have demonstrated therapeutic benefit, but preparation is labor-intensive and expensive. Lubricating preparations provide only temporary symptomatic relief.
- To avoid toxicity from preservatives (eg, benzalkonium chloride), preservative-free, small-dose units are recommended. In addition, lubricating ointments play an important role in moistening the ocular surface during sleep when tear production is decreased. Using lubricating ointment during the day can significantly blur vision. Sustained release lubricant preparations (eg, Lacrisert) were designed to dissolve slowly over a 12-hour period; however, problems of blurry vision and displacement occurred.
- Existing tears of the patient can be conserved by using punctal occlusion to decrease tear drainage. Additionally, a small lateral tarsorrhaphy can decrease the ocular surface area and provide significant relief. Humidification of the environment also significantly improves patient comfort. Humidification can be achieved by wearing swimmer's goggles or taping a plastic shield or wrap over the eyelids. Hydrophilic bandage lenses have been used for decades in the treatment of dry eye and still have a role; however, prophylactic antibiotic drops must be used concurrently. In some cases, short-term results have been achieved with amniotic membranes, particularly in the presence of active corneal ulceration.
- Agents to increase tear secretion, such as bromhexine and 3-isobutyl 1-methylxanthine (IBMX), have been tried outside of the United States. No decrease in rose bengal staining or subjective improvement in ocular irritation was noted with the use of bromhexine. Agents to stimulate muscarinic receptors (pilocarpine and cevimeline) have been approved by the US Food and Drug Administration (FDA) for oral use.
- Cyclosporin A, a powerful suppressor of T-cell function, has been evaluated for treatment of Sjögren syndrome. In one study, oral cyclosporin A (5 mg/kg/d) versus placebo was used in a double-masked trial for treatment of primary Sjögren syndrome. A subjective improvement of dry mouth symptoms occurred in most patients; however, only 20% of patients noted improvement in ocular irritation. No difference in aqueous tear production evaluated by Schirmer testing was reported between the 2 groups.
- The importance of T cell activation in the development of Sjögren syndrome has enabled use of successful therapeutic modalities based on inhibition of T cell activation. A pilot trial of 1% cyclosporin A ophthalmic ointment showed marked subjective improvement of symptoms when compared to placebo. Patients treated with topical cyclosporin A had less ocular surface rose bengal staining than control subjects; however, there was no difference in Schirmer test values or tear break-up times between the 2 groups. Topical 2% cyclosporin A solution has been reported to successfully treat paracentral corneal ulcers in patients with rheumatoid arthritis and secondary Sjögren syndrome. Cyclosporin A functions as a secretagogue for the lacrimal gland and also inhibits T cell activation, thereby limiting lymphocyte-induced apoptosis of acinar cells. Apoptosis-related markers were found to decrease in conjunctival epithelium after 6 months of treatment with topical cyclosporin A. Topical cyclosporin A is FDA-approved as a treatment of dry eye.
- It was hypothesized that systemic use of corticosteroids or androgen hormones may suppress the immune-mediated component of lacrimal gland dysfunction present in Sjögren syndrome and improve lacrimal gland secretory function. However, a 6-month trial with oral prednisone, in which patients received 30 mg on alternate days, demonstrated no improvement in functional or histological parameters in primary Sjögren syndrome. It was therefore concluded that the risks of long-term corticosteroid use outweigh the possible benefits.
- In 1985, Tseng et al reported the use of tretinoin (all trans -retinoic acid) ointment for treating various dry eye conditions, including keratitis sicca associated with Sjögren syndrome. The trial was not randomized. All research subjects reported symptomatic improvement and demonstrated decreased rose bengal staining and reduced squamous metaplasia. These findings, however, were not duplicated in a multicenter, placebo-controlled, double-masked trial. In fact, the double-masked trial failed to find a beneficial effect of tretinoin.
- A publication by Spiteri et al demonstrated significant improvement in ocular comfort in patients with dry eye symptoms with and without Sjögren syndrome after using a novel device designed to promote meibomian sebum release into the tear film in response to thermal energy.4
- For the systemic component as well as for the treatment of local immune effects, modification of the immune response with methotrexate, antimalarials, cyclophosphamide, leflunomide, or TNF antibody has been advocated. A pilot study and 1-year follow-up open trial with infliximab, a monoclonal antibody to TNF-alpha, demonstrated improvement in all tested objective and subjective measures of Sjögren syndrome disease activity. However, a follow-up randomized, double-blind, placebo-controlled trial with infliximab and etanercept, a human TNF-alpha-p75 receptor, demonstrated no benefit. Further studies of TNF-alpha antibodies are therefore needed to determine therapeutic effect. Systemic immunosuppressive agents may be necessary to improve tear production and to resolve severe keratoconjunctivitis in recalcitrant primary or secondary Sjögren syndrome.
- Although many animal models have been studied, no clinical gene transfer studies have been performed on patients with Sjögren syndrome. Recombinant serotype 2 adeno-associated virus (rAAV2) vectors have shown promise as vectors for gene therapy in mouse models of Sjögren syndrome. Future therapeutic modalities may include local delivery of an antiapoptotic or immunomodulatory transgene to reduce lacrimal gland inflammation.
Consultations
- A consultation with an internist or a rheumatologist may be warranted if a systemic autoimmune process is suspected.
- Patients with Sjögren syndrome have a higher incidence of dental and gynecological problems and should be seen for routine dental and gynecological care.
Medication
Artificial tears and lubricating ointments are widely available as nonprescription items. Individual formulations have proprietary pH, retention time, osmolarity, and viscosity characteristics. In general, these therapies are available compounded with preservatives or in a nonpreserved sterile state. For individuals who are sensitive, nonpreserved preparations are frequently selected. Most practitioners believe that the use of liquid tear substitutes with preservatives 4-6 times a day is reasonable, but, at higher usage levels, nonpreservative forms may provide less ocular surface toxicity over the long term.
Oral omega-6 essential fatty acids have been demonstrated to improve signs of ocular surface dryness and associated symptoms of ocular discomfort in Sjögren syndrome.
Tretinoin was found to be effective in increasing comfort and reducing rose bengal staining in squamous metaplasia in one study. Numerous subsequent studies have failed to confirm any positive benefit of this medication when used independently or in conjunction with surface lubricants.
Lacriserts in the form of small soluble rods can be placed in the inferior fornix and are expected to dissolve and biodegrade over a 12-hour period. This form of therapy is infrequently used because of problems associated with insertion, comfort, blurred vision, and the tendency for displacement.
Bromhexine and IBMX are used outside of the United States. Although they are available in Europe, no documentation exists that their use is associated with subjective or objective improvement. The mode of action is to increase lacrimal gland secretion directly. Oral pilocarpine has been demonstrated to increase the number of goblet cells and to improve the overall health of the conjunctival epithelium in Sjögren syndrome as evidenced by impression cytology. This may account for subjective reports of reduced ocular discomfort in Sjögren syndrome after 1-2 months of oral pilocarpine treatment. Oral pilocarpine has been approved by the FDA for use in the treatment of Sjögren syndrome.
Topical NSAIDs should be used with caution in patients with Sjögren syndrome due to demonstrated reduction of corneal sensitivity in normal and dry eye patients and risk of corneal melting.
Immunosuppressants
Cyclosporin A has been used orally to suppress T-cell function in patients who have had organ transplants. In Sjögren syndrome, its use is experimental and reports have not been encouraging. Cyclosporin A 1% or 2% in liquid or ointment form has been used topically following the initial report that its use increased lacrimal gland function in dogs.
Cyclosporin A (Sandimmune, Neoral)
Acts to suppress T-cell formation and, while not currently FDA approved, has been used clinically to increase lacrimal gland function in Sjögren syndrome.
Until the FDA approved formulation is available, the drug must be compounded as a nonpreserved agent thereby increasing the risk for secondary infection. Restasis, which contains a fixed dose of cyclosporin A, has recently been approved for topical instillation.
Adult
Apply 1% or 2% solution (in olive oil or corn oil); frequency not established; 2-6 times/d suggested; for Restasis formulation, bid application advocated; several weeks necessary for effects to become apparent
Pediatric
Not established
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO
Corticosteroids
For many years, systemic corticosteroids have been used in a variety of inflammatory conditions. Due to limited efficacy and high incidence of complications, they are not widely used in Sjögren syndrome. Topical corticosteroids are widely available in a variety of dosages, often combined with antibiotics and preservatives, and may be useful for short-term treatment of ocular surface inflammatory conditions. They are usually available in 5, 10, or 15 mL dispensers or in 1/8 ounce ointment form.
Prednisolone (Pred Forte)
Not advocated for long-term use in Sjögren syndrome. Acute episodes of ocular surface inflammation or secondary uveitis may require short-term or periodic usage.
Adult
1-2 gtt 1-6 times/d
Pediatric
Not established; 1-4 gtt/d suggested
None reported
Documented hypersensitivity; viral, fungal, or tubercular infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypertension; known to cause cataract formation with long-term use; suspect fungal infection in any persistent corneal ulceration where a corticosteroid has been used or is in use (obtain fungal cultures when appropriate)
More on Sjogren Syndrome |
| Overview: Sjogren Syndrome |
| Differential Diagnoses & Workup: Sjogren Syndrome |
 Treatment & Medication: Sjogren Syndrome |
| Follow-up: Sjogren Syndrome |
| References |
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Further Reading
Keywords
SS, keratoconjunctivitis sicca, KCS, xerostomia, dry mouth, dry eyes, autoimmune disorder, rheumatoid arthritis, systemic lupus erythematosus
