Sjogren Syndrome Guidelines

Updated: Apr 07, 2020
  • Author: Sriya K Ranatunga, MD, MPH; Chief Editor: Herbert S Diamond, MD  more...
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Guidelines

Guidelines Summary

In 2016, the Sjögren’s Syndrome Foundation (SFF) published clinical practice guidelines for Sjögren syndrome patients in the United States. [100] The guidelines note that treatment goals remain as follows:

  1. Symptom palliation
  2. Prevention of complications
  3. For rheumatologists, proper selection of patients for immunosuppressive therapy

Dry mouth

Recommendations (and their strength) for Sjögren syndrome patients with dry mouth include the following:

  • Topical fluoride should be used in for caries prophylaxis (strong)
  • Saliva can be increased through gustatory, masticatory stimulation, sugar-free lozenges and/or chewing gum, xylitol, mannitol, and the prescription medications pilocarpine and cevimeline (weak)
  • Chlorhexidine administered by varnish, gel, or rinse may be considered in patients with a high root caries rate (weak)
  • Nonfluoride remineralizing agents may be considered as an adjunct therapy in patients with a high root caries rate (moderate)

Dry eye

For dry eye disease, recommendations vary according to whether meibomian gland disease is present and by the severity of eye involvement, which is determined mainly by the presence or absence of ocular surface staining and the staining pattern.

Aqueous deficiency without meibomian gland disease

For severity 1 disease, recommendations are as follows:

  • Education and modification of the environment or diet
  • Elimination of offending systemic medication
  • Artificial tears, gels, ointments

For severity 2 disease, recommendations are as follows:

  • Omega 3 essential fatty acid supplement
  • Anti-inflammatory therapy with cyclosporine
  • Anti-inflammatory therapy with pulse steroids
  • Punctal plugs
  • Secretagogues
  • Moisture chamber spectacles

For severity 3 disease, recommendations are as follows:

  • Topical autologous serum
  • Contact lenses
  • Permanent punctal occlusion

For severity 4 disease, recommendations are as follows:

  • Systemic anti-inflammatory medication
  • Eyelid surgery

Aqueous deficiency with meibomian gland disease

For severity 1 disease, recommendations are as follows:

  • Education and modification of the environment or diet
  • Elimination of offending systemic medication
  • Artificial tears with lipid component
  • Eyelid therapy: warm compress, massage

For severity 2 disease, recommendations are as follows:

  • Omega 3 essential fatty acid supplement
  • Anti-inflammatory therapy with cyclosporine
  • Anti-inflammatory therapy with topical steroids
  • Topical azithromycin
  • Liposomal spray
  • Possible oral doxycycline
  • Expression of Meibomian glands
  • Punctal plugs
  • Secretagogues
  • Moisture chamber spectacles

For severity 3 disease, recommendations are as follows:

  • Topical autologous serum
  • Contact lenses
  • Permanent punctal occlusion
  • LipiFlow pulsed thermal compression
  • Probing of meibomian gland

For severity 4 disease, recommendations are as follows

  • Systemic anti-inflammatory medication
  • Eyelid surgery

Inflammatory musculoskeletal pain

The SFF guidelines advise that physicians consider the individual patient’s circumstances when weighing risks and benefits of each therapy. Insufficient evidence exists on the effectiveness of disease-modifying antirheumatic drugs (DMARDs) in the treatment of inflammatory musculoskeletal pain in primary Sjögren syndrome, so recommendations were formulated on the basis of expert opinion as guided by the consensus group process.

The following recommendations are listed in order of preference for use in the treatment of inflammatory musculoskeletal pain in primary Sjögren syndrome; if a therapy is insufficiently effective, the physician is advised to try the next recommendation in sequence, and so on:

  1. Hydroxychloroquine; first-line treatment
  2. Methotrexate
  3. Hydroxychloroquine plus methotrexate
  4. Short-term (1 month or less) corticosteroids (15 mg or less a day); long-term corticosteroids (≤15 mg/d for more than 1 month) may be useful, but efforts should be made to find a steroid-sparing agent as soon as possible
  5. Leflunomide
  6. Sulfasalazine
  7. Azathioprine (may be a better choice than leflunomide or sulfasalazine in patients with major organ involvement)
  8. Cyclosporine

 Fatigue

The only strongly recommended treatment of fatigue in Sjögren syndrome was exercise.  Hydroxychloroquine may be considered in selected situations

The guidelines include strong recommendations against the use of the following for fatigue:

  • Dehydroepiandrosterone (DHEA)
  • Etanercept
  • Infliximab

Insufficient evidence to issue a recommendation was found for the following therapeutic options for fatigue:

  • Interleukin-1 inhibition (anakinra)
  • Azathioprine
  • Mycophenolate
  • Zidovudine
  • Doxycycline
  • Lamivudine
  • Leflunomide
  • Abatacept
  • Belimumab
  • Epratuzumab

Biological Therapies

The guidelines advise against use of tumor necrosis factor–alpha (TNF-α) inhibitors to treat sicca symptoms in patients with primary Sjögren syndrome. If TNF-α inhibition therapy is used for rheumatoid arthritis or other related overlap conditions in patients with Sjögren syndrome, health care providers should consider and monitor for the following:

  • Lymphoma and other malignancies (risk for non-Hodgkin is elevated)
  • Serious infections, including tuberculosis
  • Invasive fungal infections
  • Hepatitis B reactivation
  • Hepatotoxicity
  • Heart failure
  • Cytopenias
  • Hypersensitivity
  • Serious infusion reactions
  • Demyelinating disease

Rituximab

Rituximab may be considered as a therapeutic option for the following indications in patients with primary Sjögren syndrome:

  • Keratoconjunctivitis sicca (KCS), in patients for whom conventional therapies (eg, topical moisturizers, secretagogues, anti-inflammatory drugs, immunomodulators, punctual occlusion) have proven insufficient
  • Xerostomia, in patients with primary Sjögren syndrome with some evidence of residual salivary production and clinician-determined significant evidence of oral damage, in whom conventional therapies, including topical moisturizers and secretagogues, have proved insufficient

Rituximab may be considered as a therapeutic option for adults with primary Sjögren syndrome and any or all of the following systemic manifestations:

  • Cryoglobulinemia associated with vasculitis
  • Vasculitis
  • Severe parotid swelling
  •  Inflammatory arthritis
  • Pulmonary disease
  • Peripheral neuropathy, especially mononeuritis

Patients and health care providers should be aware that, although uncommon, significant harms may be associated with the use of rituximab and should exercise caution and observe for the following when using rituximab in patients with Sjögren syndrome:

  • Infusion reactions
  • Tumor lysis syndrome in patients with non-Hodgkin lymphoma
  • Progressive multifocal leukoencephalopathy
  • Hepatitis B reactivation with possible fulminant hepatitis
  • Severe mucocutaneous reactions
  • Infections
  • Bowel obstruction and perforation
  • Cardiac arrhythmias and angina
  • Cytopenias
  • Serious bacterial, viral, or fungal infections

Other recommendations regarding rituximab included the following:

  • Particularly careful consideration of risk versus benefit is necessary in pregnant and nursing patients
  • Live vaccines should be avoided in patients taking rituximab

European League Against Rheumatism guidelines

In 2019, the European League Against Rheumatism (EULAR) published guidelines on the management of Sjögren syndrome with topical and systemic therapies. [101]  EULAR recommends that patients with Sjögren syndrome be managed at, or in close collaboration with, centers of expertise following a multidisciplinary approach. Specific recomendations are listed below.

Dry mouth

Baseline evaluation of salivary gland function, including measurement of whole salivary flows, and exclusion of unrelated conditions, is recommended before starting treatment for oral dryness.        

The preferred first therapeutic approach for oral dryness according to salivary gland function may be as follows:

  • Mild dysfunction - Nonpharmacological stimulation (eg, sugar-free acidic candies, lozenges, xylitol, sugar-free chewing gum)
  • Moderate dysfunction - Pharmacological stimulation (eg, pilocarpine, cevimeline; anetholtrithione, bromhexine, N-acetylcysteine in cases of intolerance or non-response)       
  • Severe dysfunction - Saliva substitution  

The guidelines recommend against using any of the following for oral dryness:

  • Hydroxychloroquine
  • Oral glucocorticoids
  • Immunosuppressive agents 
  • Rituximab                            

Dry eyes

The first-line therapeutic approach to ocular dryness includes the use of artificial tears and ocular gels/ointments. Refractory/severe ocular dryness may be managed in stepwise fashion, as follows:

  1. Topical ocular non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids may be prescribed by ophthalmologists as a short-term therapeutic approach (maximum 2–4 weeks); if no response or intolerance, then
  2. Topical cyclosporine; if no response or intolerance, then
  3. Serum eye drops; if no response or intolerance, then 
  4. Rescue therapies - Oral muscarinic agonists or plug insertion

Fatigue and/or pain:

  • Concomitant diseases should be evaluated in patients presenting with fatigue/pain, whose severity should be scored using specific tools (eg, EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI], Profile of Fatigue, Brief Pain Inventory).
  • Consider analgesics or other pain-modifying agents for musculoskeletal pain, considering the balance between potential benefits and side-effects.      

Systemic disease:

  • Treatment of systemic disease should be tailored to organ-specific severity using the EULAR Sjögren's syndrome disease activity index (ESSDAI) definitions.
  • Glucocorticoids should be used at the minimum dose and length of time necessary to control active systemic disease (eg, pulses of methylprednisolone followed by doses of 0.5 mg/kg/d or lower as induction therapy in severe presentations, and doses< 0.5 mg/kg/d in moderate/less-severe presentations, with a final target of withdrawing glucocorticoids in patients with inactive disease as soon as possible or at least trying to target a maintenance dose of 5 mg/daily or less with the aid of glucocorticoid-sparing immunosuppressive agents).
  • Immunosuppressive agents (eg, leflunomide, methotrexate, azathioprine, mycophenolate, cyclophosphamide) should be mainly used as glucocorticoid-sparing agents, with no evidence supporting the choice of one agent over another.            
  • B-cell–targeted therapies (eg, rituximab, epratuzumab, belimumab) may be considered in patients with severe, refractory systemic disease.
  • The systemic organ-specific therapeutic approach may follow, as a general rule, the sequential (or combined) use of glucocorticoids, immunosuppressive agents, and biologics.
  • Treatment of B-cell lymphoma should be individualized according to the specific histological subtype and disease stage.