What is the recommended management for Sjögren syndrome, including symptomatic treatment of dryness, systemic therapy, and monitoring for complications?

Management of Sjögren Syndrome

The management of Sjögren syndrome requires a strict separation between symptomatic treatment of sicca symptoms using topical therapies and systemic immunosuppressive therapy reserved exclusively for active systemic disease as measured by ESSDAI, with the critical error being the use of systemic immunosuppression for dryness alone. 1

Initial Assessment and Risk Stratification

Before initiating any treatment, perform objective measurement of glandular function rather than relying on subjective symptoms, as environmental and personal stressors can create a mismatch between perceived and actual glandular dysfunction 2:

• Measure unstimulated and stimulated whole salivary flows before treating oral dryness 2
• Quantify tear production using Schirmer test and ocular staining score 1
• Assess systemic disease activity using ESSDAI to determine if immunosuppression is warranted 1, 3
• Screen for high-risk features requiring enhanced surveillance: persistent salivary gland swelling, vasculitis with palpable purpura, lymphadenopathy, low complement levels (especially C4), monoclonal gammopathy, cryoglobulins, and cytopenias 1, 4

Management of Sicca Symptoms (Topical Approach)

Ocular Dryness

First-line treatment consists of artificial tears containing methylcellulose or hyaluronate 1:

• Use preservative-free formulations for frequent application 1
• Add ocular gels or ointments for nighttime use 3
• For refractory or severe cases, escalate to topical cyclosporine drops or autologous serum eye drops 1, 3

Oral Dryness (Severity-Based Algorithm)

The therapeutic approach depends on objective salivary flow measurements 2:

Mild glandular dysfunction (residual salivary function present):

• Non-pharmacological stimulation is first-line: sugar-free acidic candies, xylitol lozenges, or sugar-free chewing gum 2, 1
• Frequent sips of water 3

Moderate glandular dysfunction:

• Pharmacological stimulation with muscarinic agonists: pilocarpine or cevimeline 1, 3, 5
• These cholinergic agents are the cornerstone of current therapy 5

Severe glandular dysfunction (minimal residual function):

• Saliva substitutes: oral sprays, gels, or rinses with neutral pH containing fluoride and electrolytes to mimic natural saliva 2, 1

Preventive Dental Care

• Intense oral hygiene protocols 5
• Prevention and treatment of oral infections, particularly candidiasis 2, 5

Management of Constitutional Symptoms

Before treating fatigue and pain, systematically evaluate for concomitant conditions that may be contributing: fibromyalgia, depression, hypothyroidism, or other overlapping syndromes 1, 3:

• For musculoskeletal pain, use analgesics following the WHO analgesic ladder 1
• Consider hydroxychloroquine for fatigue and arthralgias, though evidence for efficacy is limited 1
• Short-term moderate-dose glucocorticoids may be used for acute pain flares 1

Management of Active Systemic Disease

Critical Decision Point

Systemic immunosuppression should NEVER be used for sicca symptoms or isolated hyperglobulinemia—it is reserved exclusively for active systemic disease as defined by ESSDAI 1, 4:

Sequential Two-Stage Therapeutic Regimen

Stage 1: Induction of Remission

• Glucocorticoids are first-line for active systemic disease, using the minimum effective dose for the shortest duration necessary 1, 3, 4
• Tailor treatment to organ-specific severity using ESSDAI definitions 1, 3
• Perform careful organ-by-organ evaluation of both severity and organ damage, as not all patients with active systemic disease require systemic therapy 2

Stage 2: Maintenance of Remission

• Implement glucocorticoid-sparing agents early: cyclophosphamide, azathioprine, methotrexate, leflunomide, or mycophenolate mofetil 1, 3, 4
• The specific agent and duration should be decided case-by-case due to lack of comparative data 2

Refractory Disease

For severe, refractory systemic disease, consider rituximab (B-cell targeted therapy) 1, 3, 5:

• Particularly indicated when associated with cryoglobulinemia, vasculitis, or lymphoma risk 4
• Emerging evidence supports its use for both glandular and extraglandular manifestations 5

Organ-Specific Considerations

Pulmonary involvement: Short courses of systemic steroids, bronchodilators, and/or inhaled corticosteroids 1

B-cell lymphoma: Individualized treatment according to histological subtype and disease stage, requiring oncology consultation 1, 3

Neurological manifestations: Require multidisciplinary care with neurology involvement 1, 3

Surveillance and Monitoring

Active clinical surveillance for lymphoproliferative complications is essential, particularly in high-risk patients 1:

• Monitor complement levels (C3, C4), with decreased C4 at diagnosis indicating higher lymphoma risk 1, 4
• Serial assessment for new lymphadenopathy, persistent salivary gland swelling, or cytopenias 1
• Cryoglobulins and hypocomplementemia are the main prognostic markers for severe disease 4

Multidisciplinary Care Requirements

Assemble a care team including 1:

• Rheumatologist or autoimmune disease specialist as coordinator
• Ophthalmologist for refractory ocular disease
• Dentist for preventive oral care
• Pulmonologist for respiratory manifestations
• Oncologist when lymphoproliferative complications are suspected

Preventive Measures

• Strongly recommend smoking cessation for all patients 1
• Administer influenza and pneumococcal vaccination 1
• Monitor for side effects of immunosuppressive medications 1

Critical Pitfalls to Avoid

The most dangerous error is confusing treatment of sicca symptoms with systemic disease—these require fundamentally different approaches 1, 3:

• Never use systemic immunosuppression for sicca symptoms alone 1, 4
• Do not base oral dryness treatment on subjective feelings without objective salivary flow measurement 2, 1
• Avoid prolonged glucocorticoid use without implementing steroid-sparing strategies 1, 3
• Do not treat hyperglobulinemia itself—treat the underlying systemic disease activity using ESSDAI-guided therapy 4
• Never overlook the need for multidisciplinary care, especially for complex manifestations like neuropathy or interstitial lung disease 1, 3