What is the recommended workup and management for a patient with suspected Sjogren's (Sjogren's syndrome) disease?

Sjögren's Syndrome Workup and Management

Initial Diagnostic Workup

All patients with suspected Sjögren's syndrome should undergo serologic testing for anti-SSA/Ro and anti-SSB/La antibodies, ANA, and RF, combined with objective assessment of lacrimal and salivary gland function. 1

Essential Laboratory Testing

• Serologic panel: Anti-SSA/Ro, anti-SSB/La, ANA, and rheumatoid factor are the traditional biomarkers 1, 2
• Novel biomarkers: Consider testing for antibodies to salivary gland protein-1 (SP-1), parotid secretory protein (PSP), and carbonic anhydrase VI (CA-6), which may detect early disease when traditional biomarkers are negative 2, 3
• The Sjö® test incorporates both traditional and novel biomarkers, providing greater sensitivity and specificity than traditional testing alone 2, 3

Ocular Assessment

• Objective tests required: Tear break-up time, ocular surface dye staining, Schirmer test, and tear osmolarity 4
• Tear film stability assessment: Evaluate tear osmolarity, degree of lid margin disease, and ocular surface damage 4
• Differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye, as ADDE warrants further SS workup 3

Salivary Gland Assessment

• Measure whole salivary flows to objectively assess gland function 4
• Salivary scintigraphy may be considered for functional evaluation 4
• Minor salivary gland biopsy is not routinely required but may be considered when diagnosis remains uncertain after non-invasive testing 1

Pulmonary Screening

• Baseline chest radiography is recommended for all patients with suspected or confirmed Sjögren's syndrome 4
• Baseline complete pulmonary function tests (PFTs) should be considered even in asymptomatic patients to identify subclinical disease 4
• For patients with respiratory symptoms (chronic cough >8 weeks, dyspnea), obtain complete PFTs and high-resolution CT (HRCT) with expiratory views 5, 6

Systemic Evaluation

• Monitor for red flags: Unexplained weight loss, fevers, night sweats, lymphadenopathy, and/or parotitis warrant further investigation for lymphoma or systemic complications 1, 4
• Consider HRCT chest scan rather than plain chest X-ray for patients with concerning features 1
• PET scan and biopsy should be obtained for patients with lymphadenopathy, growing lung nodules, and/or progressive cystic lung disease 1

---

Management of Sicca Symptoms

Ocular Dryness

First-line therapy consists of artificial tears containing methylcellulose or hyaluronate at least twice daily, with frequency increased based on symptoms. 6

• Preservative-free formulations are mandatory for patients requiring four or more applications daily 6
• Ophthalmic ointments should be used before bedtime for overnight symptom control 6
• For refractory cases: Topical cyclosporine A is recommended when artificial tears fail 6, 1
• Autologous serum eye drops may be considered for persistent symptoms 6

Oral Dryness

• Mild salivary dysfunction: Sugar-free gum and frequent sips of water 6
• Moderate dysfunction: Pharmacological stimulation with muscarinic agonists (e.g., pilocarpine, cevimeline) 6
• Severe dysfunction with no salivary output: Saliva substitution products 6

---

Management of Airway Disease

Chronic Cough Evaluation

Approximately 38% of Sjögren's patients develop chronic cough, requiring systematic evaluation if persisting >8 weeks 5, 6

Evaluation algorithm:

1. First assess common causes: Asthma, gastroesophageal reflux disease, upper airway cough syndrome, non-asthmatic eosinophilic bronchitis 5, 6
2. Then evaluate Sjögren's-specific complications: Xerotrachea, ILD, bronchiolitis, bronchiectasis, and pulmonary lymphoma 5

Xerotrachea (Dry Trachea)

• Empirical humidification is recommended after exclusion of other causes 5, 6
• Trial of secretagogue and/or guaifenesin 5, 6

Asthma/COPD

• Manage with inhaled corticosteroids and beta-agonists as mainstay therapy 5, 6
• Critical caveat: Avoid anticholinergics as they worsen drying of secretions 5, 6

Small Airway Disease/Bronchiolitis

Time-limited empiric therapy for newly diagnosed disease includes: 5

• Short course of systemic steroids for 2-4 weeks with repeat spirometry to assess reversibility, especially if uncontrolled asthma is suspected 5
• Nebulized or inhaled short/long-acting bronchodilators and/or inhaled corticosteroids if physiological obstruction is present 5
• Azithromycin 250 mg three days per week for 2-3 months for persistent, nonreversible, symptomatic bronchiolitis 5, 6

Bronchiectasis

Treat similarly to primary or secondary bronchiectasis of other etiologies: 5, 6

• Mucolytic agents/expectorants 5, 6
• Nebulized saline or hypertonic saline 5, 6
• Oscillatory positive expiratory pressure 5, 6
• Postural drainage 5, 6
• Mechanical high-frequency chest wall oscillation therapies 5, 6
• Chronic macrolides in those without non-tuberculous mycobacterium colonization or infection 5, 6

---

Management of Interstitial Lung Disease (ILD)

Diagnostic Workup for Suspected ILD

• HRCT with expiratory views is strongly recommended 5
• Oximetry testing as part of initial evaluation 5
• Baseline PFTs must include lung volumes by body plethysmography, spirometry, diffusing capacity, and oxygen saturations at rest and exercise 5
• Surgical lung biopsy is NOT routinely recommended but may be considered after multidisciplinary review for suspected neoplastic/lymphoproliferative disorder, other cancers, amyloid, or progressive deterioration with suspected infection 5

Monitoring Strategy

• Serial PFTs every 3-6 months initially for at least 1 year to establish disease trajectory 5
• For asymptomatic or minimally impaired patients, monitor with serial PFTs and initiate pharmacotherapy only if significant decline is documented 5

Non-Pharmacological Management

• Vaccination: All patients must receive influenza and pneumococcal vaccines (Prevnar and Pneumovax) per CDC guidelines 5
• Pulmonary rehabilitation is recommended for symptomatic patients with ILD and impaired pulmonary function 5
• Long-term oxygen therapy for resting oxygen saturation <88%, PaO₂ <55 mm Hg, or <60 mm Hg with complications of chronic hypoxemia 5
• Lung transplant evaluation for advanced disease with resting hypoxia or rapidly deteriorating lung function 5

Pharmacological Treatment

• First-line for symptomatic/moderate-severe ILD: Systemic corticosteroids 6
• First-line maintenance: Mycophenolate mofetil or azathioprine 6
• Second-line maintenance for progressive fibrotic ILD: Nintedanib (antifibrotic therapy) 6

---

Management of Systemic Disease

Systemic therapies should be restricted to patients with active systemic disease, with treatment tailored to organ-specific severity using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). 6, 4

Constitutional Symptoms (Fatigue, Arthralgias, Pain)

• Evaluate for contributing conditions and use analgesics according to pain severity following the WHO pain ladder 6
• Hydroxychloroquine may be considered for fatigue and arthralgias, though evidence for efficacy is limited 6, 4
• For chronic, non-inflammatory pain: Physical activity and aerobic exercise are preferred over medications 6
• Short-term moderate-dose glucocorticoids may be considered for acute pain 6

Moderate to Severe Systemic Disease

• Glucocorticoids at minimum effective dose and duration 6
• Immunosuppressive agents (azathioprine, mycophenolate, methotrexate) as glucocorticoid-sparing agents 6
• For refractory disease: B-cell targeted therapies, particularly rituximab 6

---

Monitoring and Follow-up

Disease Activity Assessment

• Use ESSDAI to measure systemic activity 6, 4
• Use ESSPRI (EULAR Sjögren's Syndrome Patient Reported Index) to evaluate severity of dryness, fatigue, and pain 4
• A reduction of ≥3 points in global ESSDAI score is considered a therapeutic response 6

Pulmonary Monitoring

• Repeat PFTs every 6-12 months for patients with pulmonary involvement 6, 4

Lymphoma Surveillance

• Monitor for lymphoma development (occurs in 2-5% of patients) through clinical examination for lymphadenopathy and laboratory parameters 6, 4
• Red flags include unexplained weight loss, fevers, night sweats, and new or enlarging lymphadenopathy 1, 4

---

Critical Pitfalls to Avoid

• Never use anticholinergic medications as they worsen sicca symptoms 6
• Smoking cessation is mandatory for all Sjögren's patients 5, 6, 1
• Do not delay diagnosis: Dry eye with ADDE should trigger SS workup, as diagnostic delays are common and lead to increased morbidity 2, 3, 7
• Do not overlook extraglandular manifestations: SS can cause serious vision-threatening complications including corneal melt/perforation, uveitis, scleritis, retinal vasculitis, and optic neuritis 7
• Do not perform routine bronchoscopy with BAL for small airway disease; reserve for specific circumstances such as ruling out infection in immunosuppressed patients 4