What is Sjögren Syndrome in a patient with Chronic Kidney Disease (CKD)?

Sjögren Syndrome: Definition and Clinical Overview

Core Definition

Sjögren syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands—primarily the lacrimal and salivary glands—resulting in severe dryness of mucosal surfaces, particularly dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). 1, 2

Pathophysiology

• The fundamental mechanism involves chronic inflammatory cellular infiltration by lymphocytes, particularly CD4+ T cells and activated B cells, which attack and destroy the epithelium of exocrine glands 3, 4
• This lymphocytic infiltration leads to progressive glandular dysfunction and the production of autoantibodies, particularly anti-Ro/SSA and anti-La/SSB, which attack self-tissues and cause further inflammation and tissue damage 1, 5
• The histological hallmark is focal lymphocytic sialadenitis with a focus score ≥1 foci/4 mm² on minor labial salivary gland biopsy 2, 3

Epidemiology and Risk Factors

• Sjögren syndrome affects approximately 0.4% of the general population, with an annual incidence of 3.9-5.3 per 100,000 people 2
• Women are overwhelmingly affected with a 20:1 female-to-male ratio, suggesting strong hormonal influences on disease susceptibility 2, 3
• The disease predominantly affects middle-aged women, though it can occur in children, men, and the elderly 5
• Approximately 10% of patients with clinically significant aqueous deficient dry eye have underlying primary Sjögren syndrome 2, 3

Classification

• Primary Sjögren syndrome occurs alone as a distinct autoimmune entity 2, 6
• Secondary Sjögren syndrome occurs in association with other autoimmune diseases such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus 1, 2

Clinical Manifestations

Primary Sicca Symptoms

• Dry mouth (xerostomia): Need for liquids to swallow dry foods, frequent water sipping, burning mouth sensation, angular cheilitis, frequent dental cavities, and gingivitis 2
• Dry eyes (keratoconjunctivitis sicca): Foreign body sensation, eye irritation, itchiness, pain, light sensitivity, and frequent need for eye drops 2

Systemic Manifestations

• Musculoskeletal: Joint pain (arthralgias) and muscle pain (myalgias) are common 2
• Pulmonary: Chronic cough affects approximately 38% of patients, xerotrachea causing persistent dry cough, bronchiolitis, bronchiectasis, and interstitial lung disease (ILD prevalence: 10% within first year, 20% after 5 years) 2
• Neurological: Peripheral neuropathy with numbness, changed sensation, or burning pain in extremities 2
• Other: Vaginal dryness, dry skin, extreme fatigue 2
• Renal involvement: Can affect kidneys as part of systemic disease manifestations 7

Diagnostic Criteria

The American College of Rheumatology/European League Against Rheumatism classification criteria use a weighted scoring system where ≥4 points meets criteria for primary Sjögren syndrome 2:

• Anti-SSA/Ro antibody positivity: 3 points 2
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm²: 3 points 2
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4: 1 point 2
• Schirmer test result ≤5 mm/5 minutes without anesthesia: 1 point 2
• Unstimulated salivary flow rate ≤0.1 ml/minute: 1 point 2

Critical Complications and Prognosis

• Lymphoma risk: Approximately 5% of patients develop lymphoid malignancy, representing a 320 cases per 100,000 patient-years increased incidence 2, 5
• Primary Sjögren syndrome is the rheumatic disease most strongly associated with lymphoma development, with an incidence rate of 18.9% (95% CI, 9.4–37.9) 1
• Decreased C4 levels at diagnosis are associated with higher lymphoma risk and should prompt increased surveillance 1, 2
• Sjögren syndrome is a serious disease with excess mortality, mainly related to systemic involvement and lymphoma development 5

Management Approach

First-Line Symptomatic Treatment

• For dry eyes: Artificial tears and lubricating ointments as primary therapy; topical cyclosporine 0.05% for moderate to severe inflammatory dry eye 2
• For dry mouth: Saliva substitutes as first-line; pilocarpine 5 mg orally three to four times daily if inadequate response to topical measures 2, 8

Systemic Treatment

• For mild systemic manifestations: Hydroxychloroquine 200-400 mg daily and NSAIDs for joint pain and inflammation 2
• For severe, refractory systemic disease: B-cell targeted therapies, with sequential use of glucocorticoids, immunosuppressive agents, and biologics 2

Essential Co-Management

• Mandatory rheumatology consultation is essential due to the risk of systemic complications, including the 5% lifetime lymphoma risk 2
• Regular monitoring for signs of lymphoma development, particularly in patients with low C4 levels 1, 2
• Annual pulmonary function tests for patients with respiratory symptoms 2

Special Considerations in CKD Patients

• Sjögren syndrome can cause renal involvement as part of its systemic manifestations, potentially complicating pre-existing CKD 7
• Pilocarpine dosing does not require adjustment in renal insufficiency, as pharmacokinetics remain unchanged in patients with creatinine clearances ranging from 9.8 to 40.8 mL/min 8
• However, patients with hepatic impairment show 30% decreased clearance and doubled exposure, requiring dose adjustment 8
• Immunosuppressive medications used to treat Sjögren syndrome (azathioprine, mycophenolate mofetil) can cause bone marrow suppression and require careful monitoring in CKD patients 1

Key Clinical Pitfalls to Avoid

• Do not overlook Sjögren syndrome in younger patients or men despite the strong female and postmenopausal predominance 3
• Maintain high suspicion when dry eye occurs with systemic symptoms like fatigue, arthralgia, or elevated inflammatory markers 2, 3
• Do not neglect screening for lymphoma in patients who develop unexplained hematologic abnormalities or have decreased C4 levels 1
• Avoid overlooking medication-induced hematologic abnormalities in patients on immunosuppressive therapy 1
• Consider viral triggers (EBV, hepatitis C, HTLV-1, HIV) when sicca symptoms occur following infections 3