What is the diagnosis and treatment for a patient presenting with polyarthralgia and facial and limb swelling?

Diagnosis and Treatment of Polyarthralgia with Facial and Limb Swelling

The most likely diagnosis is Adult-Onset Still's Disease (AOSD), which should be treated with systemic glucocorticoids starting at approximately 20 mg/day of prednisone, with consideration of disease-modifying antirheumatic drugs if symptoms persist.

Immediate Diagnostic Priorities

Exclude life-threatening conditions first: septic arthritis, myocarditis, and acute rheumatic fever must be ruled out before pursuing other diagnoses 1, 2, 3.

Critical Clinical Features to Assess

• Fever pattern: AOSD characteristically presents with quotidian or double-quotidian fever exceeding 39°C, typically peaking in late afternoon or early evening and lasting under 4 hours 1.
• Rash characteristics: Look for an evanescent, salmon-pink, maculopapular eruption on proximal limbs and trunk; facial involvement is rare but can occur 1.
• Joint involvement: Polyarthralgia and arthritis occur in 64-100% of AOSD cases, most commonly affecting knees, wrists, and ankles with symmetric distribution 1.
• Facial swelling: This suggests systemic inflammation and possible lymphadenopathy (present in 32-74% of AOSD cases) 1.
• Morning stiffness duration: Stiffness lasting >30-60 minutes strongly indicates inflammatory arthritis rather than mechanical pain 2, 3, 4.

Physical Examination Essentials

• Document objective joint swelling (synovitis): The presence of visible or palpable swelling differentiates true arthritis from arthralgia and fundamentally alters the differential diagnosis 2, 4.
• Perform metacarpophalangeal squeeze test: Pain or difficulty making a fist with compression supports underlying inflammation 2.
• Assess for true muscle weakness: This suggests myositis rather than isolated arthralgia and requires checking troponin if present, as myocarditis can be life-threatening 1, 3.
• Examine all peripheral joints systematically: Document tenderness, swelling, erythema, warmth, and range of motion for each joint 2, 3, 4.

Differential Diagnosis Framework

High-Priority Inflammatory Conditions

Adult-Onset Still's Disease is the leading diagnosis given the triad of polyarthralgia, facial swelling, and limb involvement 1:

• Fever >39°C with quotidian pattern (95.7% of cases) 1
• Characteristic salmon-pink rash (72.7% of cases) 1
• Polyarthritis/arthralgia (64-100% of cases) 1
• Leukocytosis >10,000/µL with >80% neutrophils 1, 2
• Elevated ESR and CRP (present in virtually all patients) 1

Rheumatoid Arthritis should be considered if 5, 6, 7:

• Symmetric polyarthritis affecting metacarpophalangeal and metatarsophalangeal joints
• Morning stiffness >30 minutes
• Positive RF or anti-CCP antibodies (though absence does not exclude diagnosis)
• Progressive joint damage on imaging

Systemic Lupus Erythematosus when 2:

• Facial rash (malar or discoid pattern)
• Serositis accompanies joint symptoms
• Positive ANA with specific extractable nuclear antigens

Psoriatic Arthritis if 1:

• Current, past, or family history of psoriasis
• Nail dystrophy or dactylitis present
• Asymmetric joint involvement with DIP joint disease

Infectious Etiologies to Exclude

• Septic arthritis: Requires urgent joint aspiration if fever, chills, and markedly elevated inflammatory markers are present 2, 3.
• Acute rheumatic fever: Consider in moderate-to-high risk populations with preceding streptococcal infection; responds dramatically to salicylates within 24-48 hours 1, 2, 4.
• Lyme disease: Migratory arthritis preceded by erythema migrans in 60-80% of cases, with tick exposure history in endemic areas 2, 4.
• Arboviral infections: Severe polyarthralgia with travel to tropical/endemic regions 3, 4.

Drug-Induced Inflammatory Arthritis

Immune checkpoint inhibitor-related arthritis if patient is receiving cancer immunotherapy 1:

• Median onset 38 weeks after treatment initiation (range 1-127 weeks)
• Can present as oligoarthritis or symmetric polyarthritis
• Inflammatory markers usually very elevated
• Autoantibodies often absent (RF positive in only 20/271 cases, ACPA in 14/271) 1

Essential Laboratory Work-Up

First-Line Tests

• Complete blood count: Leukocytosis with neutrophilia >80% strongly suggests AOSD 1, 2.
• Inflammatory markers: ESR and CRP are elevated in virtually all AOSD cases, though normal values do not exclude inflammatory disease 1, 2, 3, 4.
• Comprehensive metabolic panel: Including glucose, creatinine, liver enzymes, calcium, and alkaline phosphatase 2.
• Urinalysis: To detect renal involvement 2.

Autoimmune Serology Panel

• ANA, RF, and anti-CCP antibodies: Obtain when symptoms persist >4 weeks 2, 3.
• HLA-B27: If spondyloarthritis is suspected 2, 3.
• Creatine kinase (CK): Essential if muscle weakness is present to evaluate for myositis 2, 3.
• Troponin: Check if myositis is suspected, as myocarditis can be life-threatening 1, 3.

Additional Testing Based on Clinical Context

• Serum protein electrophoresis, TSH, vitamin D: When endocrine or protein abnormalities are suspected 2.
• ANCA and tuberculosis screening: If vasculitis or infectious mimics are in the differential 2.
• Ferritin: Markedly elevated in AOSD (often >1000 ng/mL) 1.

Imaging Strategy

• Plain radiographs of affected joints: First-line imaging to detect erosions, joint damage, or metastatic lesions 2, 3.
• Chest X-ray: To evaluate for pleuritis (present in 12-53% of AOSD) or pericarditis (10-37%) 1.
• Musculoskeletal ultrasound: Can identify synovitis at point of care and aid in early detection of inflammatory arthritis 2, 3.
• MRI: Reserved for detecting bone-marrow edema and early inflammatory changes when diagnosis remains unclear 2, 3.

Treatment Algorithm

Initial Management for Inflammatory Arthritis with Objective Synovitis

Start systemic glucocorticoids immediately 2:

• Prednisone approximately 20 mg/day (median starting dose for acute inflammatory arthritis)
• Titrate according to clinical response
• After achieving improvement, taper to the lowest effective dose to minimize long-term adverse effects

For isolated mono- or oligo-arthritis 2:

• Single intra-articular glucocorticoid injection achieves rapid symptom relief
• Expect benefit within several hours to a few days

Adjunctive Pharmacologic Therapy

• NSAIDs: First-line for mild-to-moderate symptoms without objective synovitis; expect anti-inflammatory benefit within hours to days 2.
• Disease-modifying antirheumatic drugs (DMARDs): Consider if symptoms persist despite glucocorticoid therapy 1, 5, 8.
• Methotrexate: First-line DMARD for rheumatoid arthritis and can be effective in AOSD 5, 8.
• Biologic agents: Reserved for refractory cases or when DMARDs are insufficient 5, 8.

Non-Pharmacologic Interventions

• Structured physical activity and exercise programs: Provide uniform pain relief and are the most consistently effective non-pharmacologic intervention 2.
• Cognitive-behavioral therapy: Yields uniformly positive effects on pain perception and coping 2.
• Patient education, orthotics, and weight management: Address modifiable contributors to joint stress 2.

Monitoring Strategy

• Serial rheumatologic examinations and inflammatory markers (ESR, CRP): Repeat every 4-6 weeks after initiating therapy 2, 3.
• Monitor CK in addition to ESR and CRP: If myositis is in the differential diagnosis 2, 3.
• Repeat radiographs within 12 months: To monitor disease progression or response to therapy 2.

Indications for Urgent Rheumatology Referral

Refer immediately if 1, 2, 3:

• Objective joint swelling (synovitis) is present on examination
• Persistent symptoms >4 weeks without clear alternative diagnosis
• Severe pain with signs of inflammation despite initial management
• Atypical presentation with systemic symptoms, low inflammatory markers, or age <60 years
• High risk for therapy-related adverse effects requiring specialist input

Critical Clinical Pitfalls

• Do not wait for chronicity before referring: Early referral is warranted when synovitis is detected; delaying may compromise outcomes 2, 4.
• Normal ESR/CRP does not rule out inflammatory arthritis: Proceed with clinical diagnosis and consider rheumatology consultation 2, 3, 4.
• Prior NSAID use can mask migratory patterns: Take careful history of medication use before clinical evaluation, as this can obscure the classic migratory nature of acute rheumatic fever 1.
• Facial swelling is rare in typical inflammatory arthritis: This feature should prompt consideration of AOSD, systemic lupus erythematosus, or other systemic inflammatory conditions 1.
• Improvement with NSAIDs/corticosteroids but not opioids: This response pattern strongly suggests inflammatory arthritis rather than mechanical or neuropathic pain 1, 2, 4.