What is the diagnosis and management for a 75-year-old female with dry eyes and dry mouth, positive serum Antinuclear Antibody (ANA), SSA (Ro), SSB (La), and Centromere antibodies, but negative serum Double-Stranded DNA (dsDNA)?

Diagnosis: Primary Sjögren's Syndrome with Atypical Serological Profile

This patient meets diagnostic criteria for primary Sjögren's syndrome based on her clinical presentation and positive anti-SSA/SSB antibodies, scoring at least 4 points on the European-American consensus criteria, though the positive centromere antibody is unusual and warrants additional evaluation for overlap with limited cutaneous systemic sclerosis. 1, 2

Diagnostic Interpretation

Sjögren's Syndrome Confirmation

• The combination of dry eyes and dry mouth for several years with positive anti-SSA (Ro) and anti-SSB (La) antibodies strongly supports primary Sjögren's syndrome 1, 2
• Using the weighted scoring system: anti-SSA/Ro positivity scores 3 points, and clinical symptoms with objective findings would add additional points to exceed the threshold of ≥4 points required for diagnosis 1, 2
• The negative dsDNA antibody effectively rules out systemic lupus erythematosus as the primary diagnosis, as the combination of Smith antibodies with SSA antibodies would be more characteristic of SLE 3

Atypical Feature: Positive Centromere Antibody

• The positive centromere antibody is NOT typical for isolated Sjögren's syndrome and raises concern for overlap syndrome with limited cutaneous systemic sclerosis (formerly CREST syndrome) 4
• This patient may have secondary Sjögren's syndrome occurring in association with scleroderma, rather than primary disease 2, 4
• Evaluate specifically for: skin thickening (especially fingers), Raynaud's phenomenon, dysphagia, gastroesophageal reflux, and telangiectasias 4

Immediate Management Priorities

Rheumatology Referral (Urgent)

• Co-management with a rheumatologist is essential due to the atypical serological profile, potential overlap syndrome, and approximately 5% risk of lymphoma development 2, 5
• The rheumatologist should evaluate for systemic sclerosis features and determine if this represents overlap syndrome 4

Lymphoma Risk Assessment

• This patient requires monitoring for lymphoproliferative disorders, as Sjögren's syndrome carries approximately 5% lifetime lymphoma risk 2, 5
• Check complement C4 levels immediately—decreased C4 at diagnosis indicates higher lymphoma risk and requires more intensive surveillance 1, 2, 5
• Monitor for warning signs: persistent lymphadenopathy, unexplained cytopenias, constitutional symptoms (fever, night sweats, weight loss), or parotid gland enlargement 5

Comprehensive Diagnostic Workup

Objective Confirmation of Sicca Symptoms

• Schirmer test without anesthesia (abnormal if ≤5 mm/5 minutes, scores 1 point) 1, 2
• Ocular staining score with lissamine green or fluorescein (abnormal if ≥5, scores 1 point) 1, 2
• Unstimulated salivary flow rate (abnormal if ≤0.1 mL/minute, scores 1 point) 1, 2
• Consider minor salivary gland biopsy if diagnosis remains uncertain—focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² scores 3 points 1, 2

Additional Laboratory Testing

• Complete blood count with differential to assess for cytopenias 5
• Comprehensive metabolic panel to evaluate organ function 5
• Inflammatory markers (ESR, CRP) to assess disease activity 5
• Complement levels (C3, C4) for lymphoma risk stratification 1, 2
• Rheumatoid factor (often positive in Sjögren's syndrome) 3, 4

Evaluation for Systemic Sclerosis

• Nailfold capillaroscopy to assess for scleroderma-pattern changes 4
• Pulmonary function tests with DLCO to screen for interstitial lung disease 4
• High-resolution chest CT if pulmonary symptoms or abnormal PFTs 4
• Echocardiogram to assess for pulmonary hypertension 4

Treatment Algorithm

First-Line Symptomatic Management

• For dry eyes: Preservative-free artificial tears frequently throughout the day, with lubricating ointments at bedtime 1
• For moderate-to-severe dry eye: Topical cyclosporine 0.05% or lifitegrast to reduce ocular surface inflammation 1
• For dry mouth: Saliva substitutes and frequent water sipping; meticulous oral hygiene to prevent dental caries 2, 6

Tear Conservation Strategies

• Punctal plugs (start with temporary collagen plugs, then silicone if effective) to reduce tear drainage 1
• Environmental modifications: humidifiers, avoiding air conditioning/heating vents, protective eyewear outdoors 1

Systemic Pharmacotherapy

Oral Secretagogues (Moderate-to-Severe Symptoms)

• Cevimeline 30 mg three times daily is FDA-approved for Sjögren's syndrome and may have fewer systemic side effects than pilocarpine 1, 7
• Alternative: Pilocarpine 5 mg four times daily, though 40% of patients experience excessive sweating 1, 6
• These medications show greater efficacy for oral dryness than ocular dryness, but may improve visual symptoms through miosis effect 1, 6
• Monitor for contraindications: uncontrolled asthma, narrow-angle glaucoma, acute iritis 6, 7

Hydroxychloroquine (For Systemic Manifestations)

• Consider hydroxychloroquine 200 mg daily for arthralgias, myalgias, and fatigue 2
• Evidence for efficacy specifically for dry eye symptoms is weak, but it may help extraglandular manifestations 1, 2
• Requires baseline and annual ophthalmologic screening for retinal toxicity 2

Monitoring for Complications

Ocular Complications

• Watch for scleritis, sterile keratitis, uveitis, and filamentary keratitis—these require ophthalmology evaluation 1
• Severe dry eye with corneal infiltration or ulceration requires urgent ophthalmology referral 1

Systemic Complications

• Screen for extraglandular manifestations: peripheral neuropathy, interstitial lung disease, renal tubular acidosis, vasculitis 2, 4
• Annual lymphoma surveillance with physical examination focusing on lymph nodes and parotid glands 2, 5

Critical Pitfalls to Avoid

• Do not dismiss the positive centromere antibody—this requires evaluation for systemic sclerosis overlap 4
• Do not overlook lymphoma risk—establish baseline C4 levels and maintain surveillance 1, 2, 5
• Do not prescribe oral secretagogues without screening for contraindications (asthma, glaucoma) 6, 7
• Do not assume all sicca symptoms in autoimmune disease are from Sjögren's syndrome—the negative dsDNA helps exclude lupus, but overlap syndromes are common 3, 4
• Do not neglect dental care—patients require aggressive preventive strategies due to increased caries risk from xerostomia 2, 3