What is the management approach for Stills disease (Juvenile Rheumatoid Arthritis) with thyroid nodules and heart disease?

Management of Still's Disease with Thyroid Nodules and Heart Disease

Initiate an IL-1 or IL-6 inhibitor immediately upon diagnosis of Still's disease, regardless of the presence of thyroid nodules or cardiac involvement, while simultaneously implementing aggressive cardiac monitoring and standard thyroid nodule surveillance protocols. 1

Core Still's Disease Management

First-Line Biologic Therapy

• IL-1 inhibitors (anakinra) or IL-6 inhibitors should be started as early as possible when Still's disease is diagnosed, as real-world data demonstrate high rates of rapid glucocorticoid-free clinically inactive disease (CID). 1
• Early biologic initiation may decrease the percentage of patients developing a persistent disease course. 1
• Anakinra is preferred if bacterial infection remains in the differential diagnosis. 1

Treatment Targets and Timeline

The following sequential targets must be achieved 1:

• Day 7: Resolution of fever and >50% reduction in CRP
• Week 4: No fever, >50% reduction in active joint count, normal CRP, and physician/patient global assessment <20 on 0-100 VAS
• Month 3: CID with glucocorticoids <0.1-0.2 mg/kg/day
• Month 6: CID without glucocorticoids

Cardiac Disease Management in Still's Disease

Active Cardiac Monitoring

• Pericarditis occurs in 10-37% of Still's disease patients and represents a significant cardiac manifestation requiring vigilant monitoring. 2
• Echocardiography is essential to screen for pericarditis, myocarditis, and pulmonary hypertension. 1
• High-dose glucocorticoids are often required initially for pericarditis or severe systemic manifestations. 2

Critical Cardiac Complications

• Cardiac tamponade and myocarditis are rare but potentially life-threatening complications. 1, 2
• Severe cardiac involvement does NOT contraindicate IL-1 or IL-6 inhibitor use—these agents should be continued as they are the most effective disease-modifying therapies. 1
• Patients with cardiac involvement should be managed in collaboration with Still's disease expert centers. 1

Thyroid Nodule Management

Concurrent Evaluation Approach

• Thyroid nodules are common (detected in up to 65% of the general population) and most are benign, requiring only surveillance. 3
• Initial thyroid assessment should include TSH measurement and ultrasound evaluation. 3, 4
• Autoimmune thyroiditis can coexist with Still's disease, as documented in case reports. 5

Risk-Stratified Thyroid Management

• Ultrasound characteristics determine management: cystic or spongiform appearance suggests benign process not requiring additional testing. 3
• Suspicious features (solid composition, hypoechogenicity, irregular margins, microcalcifications) warrant fine-needle aspiration biopsy. 3
• Most thyroid nodules will not require biopsy and can be managed with long-term surveillance alone. 4
• Only approximately 5-10% of thyroid nodules prove malignant. 3, 4

Integration with Still's Disease Treatment

• The presence of thyroid nodules does NOT alter Still's disease treatment strategy—proceed with IL-1 or IL-6 inhibitors as indicated. 1
• Thyroid function should be monitored periodically, as systemic inflammation can affect thyroid parameters. 5

Monitoring for Life-Threatening Complications

Macrophage Activation Syndrome (MAS)

MAS occurs in 15-20% of Still's disease patients and represents the most severe complication with high mortality. 1

Consider MAS if the following develop 1:

• Persistent fever despite treatment
• Splenomegaly
• Elevated or rising serum ferritin
• Inappropriately low cell counts
• Abnormal liver function tests
• Intravascular coagulation activation
• Elevated or rising triglycerides

MAS treatment requires high-dose glucocorticoids (methylprednisolone 15-30 mg/kg/day IV, maximum 1g/infusion) plus anakinra, ciclosporin, and/or IFN-γ inhibitors. 1

Still's Disease-Related Lung Disease

• Active screening for lung disease is mandatory: search for clubbing, persistent cough, shortness of breath, and perform pulmonary function tests (pulse oximetry, DLCO measurement). 1
• High-resolution CT scan should be performed in any patient with clinical concerns. 1
• Lung disease is NOT a contraindication to IL-1 or IL-6 inhibitors—these should be continued as withdrawal risks severe flares and MAS. 1
• Some experts recommend adding T cell-directed immunosuppression in patients with lung disease, though evidence is limited. 1

Practical Algorithm

1. Confirm Still's disease diagnosis using clinical features (fever, rash, arthritis/arthralgia, elevated ferritin, IL-18, S100 proteins if available). 1

2. Immediately initiate IL-1 or IL-6 inhibitor regardless of thyroid or cardiac comorbidities. 1

3. Perform baseline cardiac evaluation with echocardiography to assess for pericarditis, myocarditis, pulmonary hypertension. 1

4. Evaluate thyroid nodules with TSH and ultrasound; proceed with risk-stratified approach based on sonographic features. 3, 4

5. Implement intensive monitoring protocol:

   • Weekly assessment initially to achieve day 7 and week 4 targets 1
   • Monthly monitoring for MAS (CBC, ferritin, LFTs, triglycerides) 1
   • Periodic pulmonary function testing and cardiac surveillance 1
   • Thyroid nodule surveillance per standard protocols 4

6. Escalate to expert center if difficult-to-treat disease, severe/recurrent MAS, or lung disease develops. 1

Critical Pitfalls to Avoid

• Do NOT delay biologic therapy due to presence of thyroid nodules or cardiac disease—early IL-1/IL-6 inhibition improves outcomes. 1
• Do NOT withdraw IL-1 or IL-6 inhibitors if lung disease develops—this risks severe flares and MAS without improving lung disease. 1
• Do NOT use glucocorticoid monotherapy long-term—this leads to significant morbidity; biologics enable glucocorticoid-free remission. 1
• Do NOT assume all thyroid nodules require intervention—most are benign and require only surveillance. 3, 4
• Do NOT miss MAS—maintain high index of suspicion with periodic screening, as it is potentially fatal. 1