Which diagnosis has the most dangerous complications?

Most Dangerous Complications of Still's Disease

Macrophage Activation Syndrome (MAS) is the most dangerous complication of Still's disease, occurring in 15-20% of patients and potentially leading to rapid clinical deterioration and death if not promptly recognized and treated. 1

Understanding Still's Disease Complications

Still's disease (encompassing both systemic juvenile idiopathic arthritis and adult-onset Still's disease) is characterized by high spiking fevers, evanescent salmon-pink rash, musculoskeletal involvement, and elevated inflammatory markers. While the disease itself can be challenging to manage, its complications can be life-threatening.

Major Life-Threatening Complications

1. Macrophage Activation Syndrome (MAS)

   • Most frequent severe complication (15-20% of patients)
   • Can occur abruptly at any time during disease course
   • Characterized by:
     • Persistent fever despite treatment
     • Splenomegaly
     • Elevated/rising serum ferritin
     • Inappropriately low blood cell counts
     • Abnormal liver function tests
     • Intravascular activation of coagulation
     • Elevated/rising serum triglycerides 1, 2

2. Cardiac Complications

   • Tamponade
   • Myocarditis
   • Can develop rapidly and lead to hemodynamic compromise 1

3. Pulmonary Complications

   • Still's disease-related lung disease
   • Pulmonary hypertension
   • Acute lung disease
   • Risk factors include younger age at onset, Down's syndrome, occurrence of MAS, and high serum IL-18 levels 1, 2

Management of MAS

Given the high mortality risk associated with MAS, prompt recognition and aggressive treatment are essential:

1. First-line treatment: High-dose glucocorticoids

   • Intravenous methylprednisolone pulses (15-30 mg/kg/day, max 1g/infusion)
   • Dexamethasone for CNS involvement (better blood-brain barrier penetration) 1

2. Additional treatments for inadequate response:

   • Ciclosporin (or tacrolimus)
   • Anakinra (at higher doses than standard, possibly intravenous)
   • IFN-γ neutralizing monoclonal antibody (emapalumab) 1

Monitoring and Prevention

To mitigate the risk of these life-threatening complications:

• Active screening and monitoring for MAS throughout the disease course
• Regular assessment of clinical symptoms and inflammatory markers
• Screening for lung disease through clinical symptoms and pulmonary function tests
• High-resolution CT scan for patients with respiratory symptoms 1, 2

Clinical Implications

The risk of severe complications persists throughout the disease course, even during periods of apparent disease control or during treatment tapering. This underscores the importance of vigilant monitoring and prompt intervention at the first sign of deterioration.

Patients with difficult-to-treat disease, severe MAS, or lung disease should be managed in collaboration with specialized Still's disease centers to optimize outcomes and reduce mortality 1, 2.

The 2024 EULAR/PReS guidelines emphasize that these severe complications can occur unexpectedly at any point in the disease course, highlighting the need for ongoing vigilance even when the disease appears well-controlled 1.