In a pregnant woman with fever and positive anti‑SSA (Ro) antibodies suggestive of Sjögren’s syndrome or systemic lupus erythematosus, what is the recommended diagnostic work‑up and management, including infection exclusion, fever treatment, glucocorticoid and hydroxychloroquine therapy, and fetal cardiac monitoring for congenital heart block?

Management of Fever with Positive Anti-SSA Antibodies in Pregnancy

Immediate Priorities

In a pregnant woman with fever and positive anti-SSA antibodies, first exclude infection as the cause of fever, then assess for underlying autoimmune disease activity (particularly SLE or Sjögren's syndrome), and immediately initiate fetal cardiac surveillance between 16-26 weeks gestation regardless of the fever etiology. 1

---

Diagnostic Work-Up

Infection Exclusion

• Rule out infectious causes first – Fever in pregnancy requires urgent evaluation for urinary tract infection, respiratory infection, chorioamnionitis, and other common pregnancy-related infections before attributing symptoms to autoimmune disease activity 1
• Obtain complete blood count, urinalysis with culture, blood cultures if indicated, and chest imaging if respiratory symptoms present 1

Autoimmune Disease Assessment

• Test for complete autoantibody panel – Beyond anti-SSA/Ro, obtain anti-La/SSB, anti-dsDNA, complement levels (C3, C4), antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2GPI), and complete metabolic panel including renal function 1
• Assess disease activity at least once per trimester using validated disease activity measures, renal function parameters, and serological markers 1
• Anti-SSA antibodies are most commonly associated with Sjögren's syndrome and SLE; approximately half of asymptomatic anti-SSA positive mothers will eventually develop symptoms of rheumatic disease 2

Antiphospholipid Antibody Testing

• Strongly test for lupus anticoagulant, anticardiolipin, and anti-β2GPI antibodies once before or early in pregnancy in all women with SLE or suspected autoimmune disease 1
• Do not repeat these tests during pregnancy as they remain stable 1

---

Fetal Cardiac Monitoring Protocol

Risk Stratification

• First pregnancy or no prior affected infant: 2% risk of complete congenital heart block (CHB), 10% risk of neonatal lupus rash, 20% risk of transient cytopenias, 30% risk of mild transient transaminitis 1, 3, 4
• After a prior affected infant: 13-18% recurrence risk for CHB 1, 3, 4
• CHB carries 20% mortality (in utero or first year of life) and >50% of survivors require permanent pacemaker 1, 3

Surveillance Schedule

• No prior affected infant: Serial fetal echocardiography every 1-2 weeks starting at 16-18 weeks through week 26 of gestation 1, 5
• Prior affected infant: Weekly fetal echocardiography from 16-18 weeks through week 26 1, 6
• Rationale for timing: CHB rarely occurs after week 26, making this the critical surveillance window 1, 3

---

Pharmacologic Management

Hydroxychloroquine (HCQ)

• If already taking HCQ, strongly continue throughout pregnancy 1
• If not taking HCQ, conditionally start it if no contraindication – HCQ reduces CHB recurrence risk and has favorable maternal-fetal safety profile 1, 3
• HCQ is recommended preconceptionally and throughout pregnancy for all anti-SSA/La positive women 1, 3

Low-Dose Aspirin

• Start low-dose aspirin (81-100 mg daily) in the first trimester for all SLE patients and those at high risk for preeclampsia (including lupus nephritis or positive antiphospholipid antibodies) 1
• This reduces risk of preeclampsia and adverse pregnancy outcomes 1

Glucocorticoid Therapy for Fever/Disease Activity

• Oral glucocorticoids (prednisone/prednisolone) can be used to manage SLE flares during pregnancy 1
• Moderate-to-severe flares may require intravenous pulse glucocorticoids, intravenous immunoglobulin, or plasmapheresis 1
• Avoid continuous high-dose glucocorticoids due to maternal and fetal harm; use pregnancy-compatible steroid-sparing medications when possible 1

Dexamethasone for Fetal Heart Block

• First- or second-degree heart block detected on fetal echo: Consider oral dexamethasone 4 mg daily for a brief course (few weeks maximum) to potentially prevent progression 1, 6, 3
• Complete (third-degree) heart block: Strongly recommend against dexamethasone as it does not reverse established CHB and exposes mother and fetus to significant risks without proven benefit 1, 6, 3
• Recent meta-analyses show no survival benefit from dexamethasone in established CHB 3

Anticoagulation (if Antiphospholipid Antibodies Present)

• Obstetric APS (prior pregnancy loss): Low-dose aspirin plus prophylactic-dose LMWH throughout pregnancy and postpartum 1
• Thrombotic APS: Low-dose aspirin plus therapeutic-dose heparin 1
• Positive aPL without APS criteria: Conditionally recommend against prophylactic heparin unless individual high-risk circumstances exist 1

---

Additional Pregnancy-Compatible Medications

For Active Disease Requiring Treatment

• Safe options during pregnancy: Azathioprine, cyclosporine A, tacrolimus 1
• Avoid: Mycophenolate, cyclophosphamide, leflunomide, methotrexate 1

---

Multidisciplinary Co-Management

• Coordinate care with maternal-fetal medicine, rheumatology, pediatric cardiology, and neonatology throughout pregnancy given complexity of autoimmune disease management and specialized fetal cardiac monitoring needs 1, 6
• Plan delivery at a center with neonatal intensive care and pediatric cardiology capabilities 7

---

Common Pitfalls to Avoid

• Do not attribute all fever to autoimmune disease activity – Infection must be excluded first as it is more common and immediately treatable 1
• Do not delay fetal cardiac surveillance – Begin at 16-18 weeks regardless of whether fever has resolved, as CHB risk is independent of current maternal symptoms 1, 5
• Do not treat established complete heart block with dexamethasone – This exposes both mother and fetus to harm without reversing the block 1, 6
• Do not continue surveillance beyond week 26 – CHB is exceedingly rare after this point and continued monitoring has low yield 1, 3
• Do not add prednisone to standard antiphospholipid syndrome therapy – No controlled studies demonstrate benefit and potential risks are significant 1