What could cause intermittent inflammatory arthralgia of the bilateral shoulders and knees with episodic dyspnea and persistent hypotension, and how should it be evaluated and managed?

Evaluation for Adult-Onset Still's Disease or Immune-Related Inflammatory Arthritis

Your symptom constellation of intermittent bilateral shoulder and knee inflammation with episodic dyspnea and hypotension requires urgent evaluation for Adult-Onset Still's Disease (AOSD), particularly given the multi-system involvement pattern. 1, 2

Immediate Diagnostic Workup Required

Critical Laboratory Tests to Order Now

• Measure serum ferritin immediately - AOSD characteristically produces extremely elevated levels (4,000-30,000 ng/mL, sometimes up to 250,000 ng/mL) that correlate with disease activity 1, 2
• Request glycosylated ferritin fraction - values <20% strongly support AOSD diagnosis and are included in the Fautrel diagnostic criteria 1
• Complete blood count with differential - look for leukocytosis >15×10⁹ cells/L with striking neutrophilia (>80% PMN), which occurs in 50% of AOSD patients 1, 2
• ESR and CRP - virtually always elevated in AOSD and help differentiate from degenerative joint disease 3, 1
• Rheumatoid factor and ANA - should be negative in AOSD, helping exclude other autoimmune conditions 1, 2

Physical Examination Priorities

• Document fever pattern - AOSD produces high-spiking fevers >39°C in 95.7% of patients, typically quotidian or double quotidian pattern peaking in late afternoon/evening 1, 2
• Examine skin carefully during fever spikes - look for evanescent salmon-pink maculopapular rash on proximal limbs and trunk (occurs in 51-87% of patients) 1, 2
• Assess for sore throat - present in 35-92% of AOSD patients 2
• Check for hepatosplenomegaly and lymphadenopathy - hepatomegaly occurs in 50-75% and lymphadenopathy in 32-74% of AOSD patients 2

Cardiovascular Assessment for Dyspnea and Hypotension

• Evaluate for orthopnea specifically - ask if breathing difficulty worsens when lying flat, as this suggests cardiac causes with elevated pulmonary venous pressure 4
• Examine for jugular venous distension, S3 heart sound, peripheral edema, and pulmonary crackles - these indicate heart failure as the cause of dyspnea 4
• Order chest radiograph - first-line test to identify pulmonary edema, pleural effusion (occurs in 12-53% of AOSD), pericardial effusion (pericarditis in 10-37% of AOSD), or cardiomegaly 4, 1, 2
• Obtain electrocardiogram - essential for detecting cardiac abnormalities and pericarditis 4

Critical Pitfalls to Avoid

Do not dismiss this as simple degenerative arthritis - the inflammatory markers (ESR, CRP) are usually very elevated in immune-related inflammatory arthritis and AOSD, clearly differentiating these from osteoarthritis 3

Do not overlook life-threatening complications - monitor for pancytopenia, which signals potentially fatal Macrophage Activation Syndrome requiring urgent immunosuppressive intervention 1

Do not attribute symptoms to medication side effects prematurely - hepatomegaly and abnormal liver biochemistry are intrinsic AOSD features in 50-75% of patients, not just NSAID effects 1

Do not miss cardiac tamponade - pericarditis can progress to tamponade, presenting with hypotension and dyspnea 1

Alternative Diagnosis: Immune Checkpoint Inhibitor Toxicity

If you are receiving cancer immunotherapy (anti-PD-1/PD-L1 or anti-CTLA-4 agents), this presentation strongly suggests immune-related inflammatory arthritis with possible cardiopulmonary toxicity. 3

• Immune-related arthritis from checkpoint inhibitors presents with oligoarthritis of large joints (knees, shoulders) and can occur months after treatment initiation 3
• Inflammatory markers are usually very elevated, differentiating this from degenerative disease 3
• Immune-related pneumonitis (grade 2-3) could explain episodic dyspnea and requires bronchoalveolar lavage to rule out infection 3
• Immune-related myocarditis, though rare, presents with dyspnea and hypotension and has high mortality - requires urgent cardiac evaluation 3

Management if Immunotherapy-Related

• NSAIDs alone are usually insufficient - most patients require systemic corticosteroids (10-20 mg prednisone for arthritis, 1-2 mg/kg methylprednisolone IV for grade 3 pneumonitis) 3
• Intra-articular corticosteroid injections are appropriate if only one or two joints affected 3
• Hold immunotherapy immediately if grade 2-3 toxicity confirmed 3

Diagnostic Criteria Application

Once exclusions complete, apply Yamaguchi Criteria (requires 5 criteria with ≥2 major): fever, arthralgia, typical rash, WBC >10,000, negative ANA and RF 1

Or apply Fautrel Criteria incorporating ferritin values: major criteria include spiking fever, arthralgia, transient erythema, pharyngitis, PMN >80%, glycosylated ferritin <20% 1