What is the diagnosis and treatment for a middle-aged patient with chronic joint pains, morning stiffness, fever, myalgia, rashes, anemia, leukopenia, thrombocytopenia, and elevated ESR?

Diagnosis: Adult-Onset Still's Disease (AOSD)

This patient's presentation of chronic joint pain, morning stiffness, fever, myalgia, rash, and pancytopenia (anemia, leukopenia, thrombocytopenia) with elevated ESR strongly suggests Adult-Onset Still's Disease, though the pancytopenia raises critical concern for macrophage activation syndrome (MAS), a life-threatening complication requiring immediate evaluation and treatment. 1

Clinical Reasoning and Diagnostic Approach

Why AOSD is the Leading Diagnosis

The constellation of findings fits AOSD remarkably well:

• Fever, rash, arthralgia/arthritis, and myalgia are cardinal features present in 82-100% of AOSD cases across major series 1
• Elevated ESR (44 mm/hr) is found in virtually all AOSD patients, while CRP can be normal in some cases despite active disease 1
• Morning stiffness with chronic joint pain affecting multiple joints is characteristic, with knees, wrists, and ankles most commonly involved (69-82% of cases) 1
• Myalgia occurs in 56-84% of AOSD patients and typically appears with fever exacerbations 1

Critical Red Flag: Pancytopenia Suggests MAS

The pancytopenia (Hgb 112, WBC 1.7, Plt 90) is highly atypical for uncomplicated AOSD and should immediately alert you to macrophage activation syndrome (MAS), which requires prompt immunosuppressive treatment to prevent mortality. 1

• Typical AOSD shows leukocytosis (50% have WBC >15×10⁹/L, 37% have WBC >20×10⁹/L), anemia of chronic disease, and reactive thrombocytosis 1
• Pancytopenia in the setting of AOSD indicates haemophagocytic syndrome/MAS, which can occur at disease onset or during flares, even in remission 1
• MAS is the most life-threatening complication of Still's disease and must be detected promptly 1

Immediate Diagnostic Workup Required

Essential Laboratory Tests to Order NOW

• Ferritin level - expect extremely high levels (4,000-30,000 ng/mL, sometimes up to 250,000 ng/mL) with 80% sensitivity when ≥5× upper limit of normal 1
• Glycosylated ferritin fraction - if available, <20% is highly specific (93%) for AOSD when combined with elevated total ferritin 1
• Complete metabolic panel including liver function tests, as 50-75% have hepatomegaly and liver enzyme abnormalities 1, 2
• Peripheral blood smear to evaluate for hemophagocytosis 1
• Triglycerides, fibrinogen, D-dimers - elevated in MAS; coagulation abnormalities can progress to DIC 1
• IL-18 levels if available - emerging as useful diagnostic marker 1

Serologic Testing

• Pending ANA - typically negative in AOSD, which helps differentiate from SLE 1, 2
• Rheumatoid factor (RF) and anti-CCP - should be negative; if positive, consider alternative diagnosis 2
• Hepatitis B, C, and tuberculosis screening before starting immunosuppression 2, 3

Imaging Studies

• Bilateral hand, wrist, and foot X-rays - look for carpal and pericapitate abnormalities typical of AOSD, which develop after 6 months with progressive ankylosis at 1.5-3 years 1
• Chest X-ray - evaluate for pleuritis (12-53% of cases) or pericarditis (10-37% of cases) 1

Differential Diagnoses to Exclude

Critical Exclusions

• Systemic Lupus Erythematosus (SLE) - can present with fever, rash, cytopenias, and elevated ESR, but typically has positive ANA, anti-dsDNA, and low complement levels 4, 5
• Hemophagocytic Lymphohistiocytosis (HLH) - primary consideration given pancytopenia; requires bone marrow biopsy if MAS suspected 1
• Infection/Sepsis - procalcitonin 0.51 is borderline elevated (normal <0.5), warranting blood cultures and infectious workup 1
• Malignancy - lymphoma or leukemia can mimic AOSD with fever, cytopenias, and elevated inflammatory markers 6
• Autoinflammatory syndromes (FMF, TRAPS, HIDS) - consider if recurrent fever attacks with family history 6

Why Not Rheumatoid Arthritis?

• RA typically shows leukocytosis, not leukopenia 2
• RA rarely presents with high spiking fevers and salmon-pink rash 2
• Thrombocytopenia is uncommon in RA; reactive thrombocytosis is more typical 2
• Morning stiffness and polyarthritis overlap, but systemic features point to AOSD 1

Treatment Algorithm

If MAS is Confirmed or Highly Suspected

Initiate high-dose corticosteroids immediately (methylprednisolone 1-2 mg/kg/day IV or prednisone 1-2 mg/kg/day PO) plus immunosuppressive agents such as cyclosporine or anakinra. 1, 7

• MAS requires prompt immunosuppressive treatment to prevent mortality from DIC, hepatic failure, or multiorgan dysfunction 1
• Monitor closely for progression: worsening cytopenias, rising ferritin, falling fibrinogen, rising D-dimers 1

If Uncomplicated AOSD Without MAS

Start prednisone 0.5-1 mg/kg/day (typically 40-60 mg daily) as first-line therapy, with plan to taper based on clinical response and inflammatory markers. 7, 8

• Corticosteroids are the mainstay of AOSD management 7, 8
• NSAIDs can be added for symptomatic relief but are insufficient as monotherapy 1
• If inadequate response or steroid-dependent, add methotrexate 15-25 mg weekly or biologic agents (IL-1 inhibitors like anakinra, IL-6 inhibitors like tocilizumab) 1

Treatment Targets and Monitoring

• Ultimate goal is drug-free remission, achievable in substantial proportion with modern therapies 1
• Monitor disease activity every 4-6 weeks with clinical assessment, ESR/CRP, ferritin, and CBC 1, 2
• Taper corticosteroids slowly once remission achieved to prevent flares 1, 8
• Screen for infections before and during immunosuppression 2, 3

Critical Pitfalls to Avoid

• Do not dismiss pancytopenia as "just part of AOSD" - it signals MAS and requires urgent intervention 1
• Do not delay treatment waiting for ANA results - AOSD is typically ANA-negative, and clinical diagnosis with ferritin is sufficient to start therapy 1
• Do not attribute fever to infection without thorough evaluation - AOSD fever is typically spiking (≥39°C) and may not respond to antibiotics 1
• Do not ignore normal CRP - ESR can be elevated while CRP remains normal in some AOSD cases 1
• Monitor for MAS throughout disease course - it can occur during remission, especially with infection triggers 1

Rheumatology Referral

Refer urgently to rheumatology given complex presentation with pancytopenia, need for immunosuppression, and risk of MAS. 1, 3

• AOSD requires specialist management for optimal outcomes 1
• MAS evaluation may require bone marrow biopsy and specialized treatment protocols 1