Urgent Evaluation for Macrophage Activation Syndrome (MAS) Complicating Still's Disease
This patient requires immediate evaluation for macrophage activation syndrome (MAS), a life-threatening complication of Still's disease, and should be treated urgently with high-dose corticosteroids while awaiting confirmatory testing. 1
Critical Diagnostic Reasoning
Why This is Likely MAS Complicating Still's Disease
The constellation of fever, rash, arthritis with elevated ESR but normal CRP is highly atypical for most inflammatory conditions and represents a critical diagnostic clue. 1 This dissociation between ESR and CRP, combined with pancytopenia, strongly suggests MAS rather than uncomplicated Still's disease, where both ESR and CRP are typically markedly elevated. 1
Key diagnostic features present:
- Spiking fever (characteristic of Still's disease) 1
- Transient rash coinciding with fever spikes 1
- Arthritis (though not mandatory for Still's disease diagnosis) 1
- Pancytopenia - a hallmark of MAS, not typical Still's disease 1
- Normal CRP despite elevated ESR - the "CRP paradox" seen when ferritin consumption occurs in MAS 1
- Renal involvement with proteinuria and casts (indicating systemic severity) 1
- Negative ANA (excludes SLE as primary diagnosis) 1
Why the Normal CRP is Diagnostically Critical
In typical Still's disease, both ESR and CRP are markedly elevated with neutrophilic leukocytosis. 1 The presence of elevated ESR with normal CRP in the context of pancytopenia suggests consumption of acute phase reactants and cytokine storm characteristic of MAS. 1 This is a red flag that demands immediate action.
Immediate Management Steps
1. Urgent Laboratory Workup (Obtain Within Hours)
Essential MAS-specific tests: 1
- Serum ferritin (expect markedly elevated >500 ng/mL, often >10,000 ng/mL in MAS)
- Triglycerides (elevated >265 mg/dL supports MAS)
- Fibrinogen (paradoxically low or falling despite inflammation)
- D-dimers (markedly elevated)
- Liver function tests (transaminitis expected)
- LDH (markedly elevated)
- Soluble IL-2 receptor/CD25 (if available)
Complete blood count with differential: 1
- Document degree of pancytopenia
- Assess for neutropenia (not neutrophilia as in uncomplicated Still's)
Renal function assessment: 1
- Serum creatinine and estimated GFR
- Urinalysis with microscopy (already showing proteinuria with hyaline and granular casts)
- 24-hour urine protein quantification
2. Bone Marrow Aspiration and Biopsy
Perform urgently to document hemophagocytosis - the pathognomonic finding of MAS showing macrophages engulfing erythrocytes, leukocytes, platelets, or their precursors. 1, 2 This should not delay treatment initiation if clinical suspicion is high.
3. Exclude Infectious Triggers
MAS can be triggered by infection even in patients with underlying Still's disease. 1 Obtain:
- Blood cultures (bacterial and fungal)
- Viral serologies including EBV PCR, CMV PCR, parvovirus B19 3, 2
- Respiratory viral panel if any respiratory symptoms
- Urine culture
4. Immediate Treatment Initiation
Do not wait for confirmatory testing if clinical suspicion is high. 1
High-dose intravenous corticosteroids: 1, 2
- Methylprednisolone 1-2 mg/kg/day IV (or pulse dose 500-1000 mg daily for 3 days in severe cases)
- MAS is rapidly fatal without treatment
Consider IVIG: 2
- 2 g/kg divided over 2-5 days
- Particularly if infection cannot be excluded
Supportive care:
- Intensive care monitoring for multiorgan failure
- Renal support if acute kidney injury progresses
- Transfusion support for severe cytopenias
Alternative Diagnoses to Exclude
ANCA-Associated Vasculitis (Less Likely)
While renal involvement with proteinuria and casts could suggest ANCA-associated vasculitis, the negative ANA makes this less likely but does not exclude it. 1 However, the pancytopenia and normal CRP are atypical for active ANCA vasculitis, where CRP is typically markedly elevated. 1
If considering vasculitis, obtain: 1
- MPO-ANCA and PR3-ANCA by ELISA (preferred over immunofluorescence)
- Chest imaging for pulmonary involvement
- Note: 10% of ANCA vasculitis patients are ANCA-negative 1
Drug-Induced Lupus or Hypersensitivity (Less Likely)
The negative ANA makes drug-induced lupus unlikely. 4 However, obtain detailed medication history for recent drug exposures that could cause fever, rash, and pancytopenia. 4
Hemophagocytic Lymphohistiocytosis (HLH) from Other Causes
MAS is essentially secondary HLH triggered by rheumatologic disease. 1, 2 Consider primary HLH or infection-triggered HLH (particularly EBV) if no evidence of Still's disease emerges. 3, 2
Critical Pitfalls to Avoid
Do not dismiss the diagnosis because CRP is normal - this is actually a diagnostic clue for MAS rather than uncomplicated inflammatory disease. 1
Do not delay treatment waiting for bone marrow results - MAS has high mortality and requires immediate corticosteroid therapy. 1
Do not assume negative ANA excludes all autoimmune disease - Still's disease is characteristically ANA-negative. 1
Do not overlook infection as a trigger - even if MAS is present, an underlying infection may have precipitated it and requires concurrent treatment. 1
Rheumatology and Hematology Consultation
Immediate consultation required with both rheumatology and hematology given the life-threatening nature of MAS and need for expert management of Still's disease. 1 This patient requires management at a center with experience in treating MAS and Still's disease. 1
Prognosis and Follow-Up
If MAS is confirmed and treated promptly, many patients achieve remission. 1 However, MAS can recur during Still's disease flares or with infections, requiring vigilant long-term monitoring. 1 The ultimate goal is drug-free remission of the underlying Still's disease, which is achievable with modern biologic therapies (IL-1 and IL-6 inhibitors). 1