What is the diagnosis and management for a patient with leukocytosis, paresthesia, abnormal arm sensations, back tingling, elevated inflammatory markers, and facial flushing?

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

The constellation of leukocytosis, paresthesias, back tingling, elevated inflammatory markers, and facial flushing strongly suggests Adult-Onset Still's Disease (AOSD), particularly when accompanied by the characteristic fever pattern and rash described in this syndrome. 1

Key Diagnostic Features Present

Your patient demonstrates several cardinal manifestations of AOSD:

• Leukocytosis with neutrophilia: AOSD characteristically produces striking neutrophilia from bone marrow granulocyte hyperplasia, with 50% of patients having peripheral leucocyte counts >15×10⁹ cells/L and 37% exceeding 20×10⁹ cells/L 1

• Markedly elevated inflammatory markers: ESR is raised in virtually all patients, and CRP is typically very elevated 1

• Facial flushing with rash: The transient erythematous (salmon pink) rash is a key diagnostic feature that often coincides with fever spikes and preferentially involves the trunk, though facial involvement occurs 1

• Paresthesias and back tingling: These musculoskeletal symptoms align with the myalgia seen in 56-84% of AOSD patients, which appears generalized and coincides with fever exacerbations 1

Diagnostic Workup Required

Immediately obtain the following laboratory tests to confirm diagnosis and exclude mimics:

• Serum ferritin level: Expect very high levels (4,000-30,000 ng/ml or even up to 250,000 ng/ml), which correlate with disease activity 1

• Glycosylated ferritin fraction: If available, levels <20% combined with fivefold serum ferritin elevation provide 43% sensitivity and 93% specificity for AOSD 1

• Complete blood count with differential: Document the degree of leukocytosis, assess for anemia of chronic disease, and check for thrombocytosis 1

• Comprehensive metabolic panel: Evaluate for hepatic involvement (present in 50-75% of patients) 1

• Autoantibody panel (ANA, RF, anti-CCP): These should be negative in AOSD; their presence suggests alternative diagnoses 1

Apply Yamaguchi criteria for diagnosis, which requires:

• Major criteria: Fever ≥39°C for ≥7 days, arthralgia, typical rash, leukocytosis ≥10,000/μL with ≥80% neutrophils 1
• Minor criteria: Sore throat, lymphadenopathy/splenomegaly, liver dysfunction, negative RF and ANA 1
• Diagnosis requires ≥5 criteria including ≥2 major criteria 1

Critical Pitfall: Macrophage Activation Syndrome (MAS)

Monitor vigilantly for MAS, the most life-threatening complication of AOSD, which can occur at onset, during treatment, or even in remission. 1

Watch for these warning signs:

• Sudden drop in white blood cell count (pancytopenia) 1
• Persistent high fever despite treatment 1
• Hepatosplenomegaly with liver dysfunction 1
• Coagulopathy or disseminated intravascular coagulation 1

If MAS is suspected, immediately check ferritin (often >10,000 ng/ml), triglycerides, fibrinogen, and consider bone marrow examination for hemophagocytosis. This requires urgent immunosuppressive treatment. 1

Management Algorithm

Initial treatment approach:

1. For moderate disease activity: Start prednisone 0.5-1 mg/kg daily (typically 40-60 mg daily for adults) 1

2. Monitor response at 1-3 month intervals with ESR, CRP, ferritin, and clinical assessment 1, 2

3. If inadequate response or steroid-dependent: Add disease-modifying therapy:

   • IL-1 inhibitors (anakinra or canakinumab) are highly effective for AOSD 1, 3
   • IL-6 inhibitors (tocilizumab) as alternative 1

4. Apply treat-to-target strategy: Adjust DMARDs dynamically based on disease activity, with ultimate goal of drug-free remission 1

5. NSAIDs alone are insufficient for controlling AOSD and should not be used as monotherapy 1

Differential Diagnoses to Exclude

Before confirming AOSD, rule out:

• Infections: Obtain blood cultures if fever present; consider endocarditis with echocardiography if murmurs detected 2
• Malignancy: Particularly lymphoma or leukemia if constitutional symptoms prominent 4, 5
• Other autoimmune diseases: Giant cell arteritis (if age >50), polymyalgia rheumatica, systemic lupus erythematosus 2
• Drug-induced conditions: Review medications, particularly immune checkpoint inhibitors if cancer history present 1

The key distinguishing feature is the combination of very high ferritin (often >5× upper limit of normal), negative autoantibodies, and the characteristic fever-rash pattern that defines AOSD. 1, 3