What is the diagnosis and treatment for an adult patient with a positive centromere antibody (CENP) test, possibly with a history of Raynaud's phenomenon?

Diagnosis and Management of Isolated Positive Centromere Antibody

Primary Diagnosis

A positive centromere antibody most strongly suggests limited cutaneous systemic sclerosis (lcSSc), occurring in 50-80% of these cases, and generally indicates a better prognosis compared to other scleroderma subtypes. 1

However, the presence of anticentromere antibody (ACA) alone does not automatically confirm systemic sclerosis—it requires careful clinical correlation and systematic evaluation for associated features.

Diagnostic Evaluation Algorithm

Initial Clinical Assessment

When ACA is detected, perform a thorough evaluation for scleroderma spectrum disorders, specifically assessing for: 1

• Raynaud's phenomenon (episodic digital color changes with cold or stress)
• Skin thickening (particularly sclerodactyly)
• Digital ulcers or pitting scars
• Telangiectasias (visible dilated blood vessels)
• Esophageal symptoms (dysphagia, reflux)

Risk Stratification Based on Clinical Context

Patients with ACA plus Raynaud's phenomenon: The simultaneous presence of Raynaud's phenomenon and anticentromere antibody predicts the occurrence of systemic sclerosis, and these patients require close monitoring as they may develop full systemic sclerosis over time. 2

Patients with ACA without Raynaud's phenomenon: The presence of anticentromere antibody alone cannot necessarily predict the development of systemic sclerosis, and these patients have a lower risk of progression. 2

Alternative diagnoses to consider: ACA can appear in other conditions including systemic lupus erythematosus (particularly with digital vasculitis), seronegative polyarthritis, and other connective tissue diseases. 3

Mandatory Screening Tests

Regardless of symptoms, all ACA-positive patients require comprehensive screening: 1

• Pulmonary arterial hypertension (PAH) screening: Echocardiography, pulmonary function testing (PFTs including spirometry and DLCO), electrocardiography, NT-proBNP, and 6-minute walking distance, as PAH is a serious late complication in ACA-positive patients 1

• Interstitial lung disease (ILD) evaluation: History, physical examination, chest radiography, PFTs, and high-resolution CT when appropriate (though anti-centromere antibodies are considered protective and decrease the likelihood of ILD development in systemic sclerosis) 4, 1

• Liver function tests: Screen for primary biliary cholangitis, which occurs in 8% of lcSSc cases, usually in those with anti-centromere antibodies; check for elevated alkaline phosphatase and assess for generalized pruritus 1

• Blood pressure monitoring: Regular checks and home blood pressure monitoring to detect scleroderma renal crisis 1

• Additional autoimmune testing: Consider extractable nuclear antibodies (anti-Smith, anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Jo-1) to identify potential overlap syndromes 1

Treatment Approach

For Patients Without Systemic Sclerosis Features

If evaluation reveals only isolated ACA positivity without clinical features of systemic sclerosis or other connective tissue disease:

• No specific immunosuppressive treatment is indicated at this time
• Annual monitoring for development of symptoms, particularly Raynaud's phenomenon and skin changes
• Lifestyle counseling: Avoid cold exposure, smoking cessation, stress management 5

For Patients With Raynaud's Phenomenon

Non-pharmacological measures (first-line for all patients): 5

• Avoidance of triggers: cold exposure, trauma, stress, smoking, vibration injury
• Proper warm clothing: coat, mittens (not gloves), hat, insulated footwear, hand/foot warmers
• Physical therapy to stimulate blood flow

Pharmacological treatment algorithm: 5

1. First-line: Nifedipine (dihydropyridine calcium channel blocker) reduces both frequency and severity of attacks in approximately two-thirds of patients 5

2. Second-line: Phosphodiesterase-5 inhibitors (sildenafil or tadalafil) when calcium channel blockers provide inadequate response; particularly valuable if digital ulcers are present 5

3. Third-line: Intravenous iloprost for severe Raynaud's unresponsive to oral therapies 5

For Patients With Digital Ulcers

• Prevention: Bosentan is most effective for preventing new digital ulcers, especially if ≥4 digital ulcers are present at baseline 5
• Healing: Intravenous iloprost or phosphodiesterase-5 inhibitors 5
• Wound care: Specialized nursing care, antibiotics only when infection is suspected, and adequate pain control 5

For Gastrointestinal Manifestations

• Esophageal dysmotility: Proton pump inhibitors and prokinetic agents 1
• Malabsorption: Monitor for and treat nutritional deficiencies 1

Additional Management Considerations

• Screen for depression: Elevated in patients with chronic diseases including systemic sclerosis 1
• Bone density scanning: For osteoporosis, which is increased in systemic sclerosis 1
• Cardiovascular risk management: Hypertension, diabetes mellitus, hyperlipidemia, and smoking cessation 1

Monitoring Strategy

For patients with ACA plus Raynaud's phenomenon: Close follow-up every 3-6 months during the first 5 years, as the risk of developing systemic sclerosis is greatest during this period. 4

For patients with isolated ACA: Annual clinical assessment and repeat screening tests as clinically indicated.

Critical Pitfalls to Avoid

• Do not assume isolated ACA equals systemic sclerosis: Clinical correlation is essential, as ACA can occur in other conditions or remain isolated without disease progression 3, 2
• Do not overlook PAH screening: PAH is a major cause of morbidity and mortality in ACA-positive patients, even those with limited cutaneous disease 4, 1
• Do not delay treatment of Raynaud's phenomenon: Early intervention can prevent digital ulcers and their complications 5
• Do not miss primary biliary cholangitis: Check liver function tests, as this association is common in ACA-positive patients 1