I have intermittent inflammatory arthritis of the shoulders and knees with episodic dyspnea—what systemic condition should I be evaluated for and what is the recommended work‑up and initial management?

Evaluation for Adult-Onset Still's Disease (AOSD)

Your pattern of intermittent shoulder and knee inflammation with episodic breathing difficulty is highly concerning for Adult-Onset Still's Disease (AOSD), a systemic autoinflammatory condition that requires urgent rheumatologic evaluation and specific diagnostic work-up. 1

Why AOSD Should Be Your Primary Concern

AOSD characteristically presents with the exact triad you describe: inflammatory arthritis affecting large joints (especially shoulders and knees), systemic symptoms, and potential pulmonary involvement causing dyspnea. 1 The intermittent "on and off" pattern you describe matches the polycyclic systemic pattern seen in approximately one-third of AOSD patients, where recurrent flares occur with complete remission between episodes. 1

Critical Diagnostic Features to Assess

You need immediate evaluation for these AOSD hallmarks:

• Fever pattern: AOSD typically causes high-spiking fevers ≥39°C (102.2°F) lasting at least 7 days, often with a quotidian (daily) pattern where fever spikes once or twice daily then returns to normal. 1 The fever often coincides with worsening joint symptoms. 1

• Rash: Look for a salmon-pink, transient, erythematous rash that appears during fever spikes and disappears between episodes, typically on the trunk. 1 However, other rash patterns including urticarial forms can occur. 1

• Sore throat: Pharyngitis is a common early symptom in AOSD. 1

• Lymphadenopathy or splenomegaly: These systemic features support AOSD diagnosis. 1

Essential Diagnostic Work-Up

Laboratory Testing (Order Immediately)

The following blood tests are critical for AOSD diagnosis:

• Serum ferritin: Markedly elevated ferritin (often >1,000 ng/mL) is a hallmark of AOSD. 1 More importantly, request glycosylated ferritin fraction if available—a level <20% is highly specific for AOSD. 1

• IL-18 and S100 proteins (calprotectin): Marked elevation strongly supports AOSD diagnosis and should be measured if available. 1

• Complete blood count: Look for neutrophilic leukocytosis (WBC >10,000 with >80% granulocytes/PMNs). 1

• Inflammatory markers: ESR and CRP are typically markedly elevated during active disease. 1

• Liver function tests: Abnormal transaminases are common in AOSD. 1

• RF and ANA: These should be negative in AOSD—their presence suggests alternative diagnoses. 1

Imaging Studies

Chest radiograph or CT scan is mandatory given your episodic dyspnea to evaluate for: 1

• Pleuritis or pericarditis: Serositis is a recognized AOSD complication. 1

• Interstitial lung disease: AOSD-associated lung disease can cause persistent cough, shortness of breath, and requires high-resolution CT for detection. 1 This is a life-threatening complication that must be actively screened. 1

• Pulmonary function tests: Including pulse oximetry and DLCO measurement should be performed if any respiratory symptoms exist. 1

Joint imaging:

• Bilateral hand, wrist, and foot X-rays to assess for erosive changes, though early AOSD may show normal radiographs. 1

• Shoulder and knee X-rays to evaluate the specific joints you describe as inflamed. 1

Diagnostic Criteria Application

Use the Yamaguchi criteria (most sensitive at 93.5%) or the newer Fautrel criteria for classification: 1

Yamaguchi requires 5 criteria with at least 2 major:

Major criteria:

• Fever ≥39°C for ≥1 week
• Arthralgia ≥2 weeks
• Typical rash
• WBC ≥10,000 with ≥80% granulocytes

Minor criteria:

• Sore throat
• Lymphadenopathy/splenomegaly
• Liver dysfunction
• Negative RF and ANA

1

Critical exclusion: Infections, malignancies, and other rheumatic diseases (especially rheumatoid arthritis, psoriatic arthritis, reactive arthritis) must be ruled out. 1

Life-Threatening Complications Requiring Immediate Recognition

Macrophage Activation Syndrome (MAS)

MAS develops in approximately 10% of AOSD patients and carries up to 6% mortality. 1 You must be screened for:

• Persistent fever despite treatment
• Splenomegaly
• Elevated or rising ferritin
• Inappropriately low blood cell counts (cytopenias)
• Abnormal liver function tests
• Elevated triglycerides
• Low fibrinogen
• Coagulopathy

1

If MAS is suspected, treatment must include high-dose glucocorticoids immediately, plus consideration of anakinra, ciclosporin, and/or IFN-γ inhibitors as part of initial therapy. 1

Respiratory Complications

Your episodic dyspnea is particularly concerning because respiratory failure is a rare but serious AOSD complication. 1 Active screening with clinical symptoms (clubbing, persistent cough, shortness of breath), pulmonary function tests, and high-resolution CT is mandatory. 1

Initial Management Strategy

Treatment Targets and Timing

The 2024 EULAR/PReS recommendations establish specific time-based targets: 1

• Day 7: Resolution of fever and reduction of CRP by >50%
• Week 4: No fever, reduction of active joint count by >50%, normal CRP
• Month 3: Clinically inactive disease with glucocorticoids <0.1-0.2 mg/kg/day
• Month 6: Clinically inactive disease without glucocorticoids

1

Pharmacologic Treatment

IL-1 or IL-6 inhibitors should be initiated as early as possible when AOSD diagnosis is established to avoid prolonged systemic glucocorticoid use. 1 These biologic agents have high evidence of efficacy and should be prioritized. 1

Traditional treatment approach (if biologics unavailable):

• NSAIDs: Only 7-15% of patients achieve disease control with NSAID monotherapy (indomethacin or naproxen preferred over aspirin). 1

• Glucocorticoids: 76-95% of patients require corticosteroids at some point. 1 Most patients need prednisone 10-20 mg/day initially, with 46-89% requiring maintenance therapy. 1

• Disease-modifying agents: May be needed for steroid-sparing effect in chronic cases. 1

Prognosis and Disease Patterns

Understanding your likely disease course is important: 1

• Monocyclic pattern (⅓ of patients): Single episode with remission within 1 year
• Polycyclic pattern (⅓ of patients): Recurrent flares with complete remission between episodes—this matches your "on and off" description
• Chronic articular pattern (⅓ of patients): Persistent joint disease that can lead to destruction; 67% in this group require joint replacement

1

Poor prognostic indicators include: shoulder involvement at disease onset (which you have), polyarthritis, and root joint involvement. 1

Critical Next Steps

1. Urgent rheumatology referral for definitive diagnosis and treatment initiation 1

2. Complete the diagnostic work-up outlined above before your rheumatology appointment if possible 1

3. Do not delay evaluation if you develop high fevers, worsening dyspnea, or signs of systemic illness—these may indicate MAS or other serious complications requiring immediate hospitalization 1

4. Document symptom patterns: Keep a diary of when joint inflammation occurs, any associated fevers, rash appearances, and breathing difficulties to help establish the diagnosis 1