# Clinical Cases: Rheumatoid Arthritis

## Case 1: Early Rheumatoid Arthritis with Positive Serology

### Patient Presentation
**Demographics:** 42-year-old woman

**Chief Complaint:** "My hands and feet have been swollen and painful for the past three months."

**History of Present Illness:**
The patient describes insidious onset of pain and stiffness affecting her fingers, wrists, and the balls of her feet bilaterally. She experiences significant morning stiffness that lasts approximately 2 hours and gradually improves with activity throughout the day. The symptoms have been progressive, and she now has difficulty making a fist, buttoning her clothes, and walking comfortably. She reports associated fatigue that is disproportionate to her activity level. She denies preceding trauma, infection, or new medications. She has lost 5 pounds unintentionally over the past two months.

**Past Medical History:**
- Hypothyroidism
- No prior joint disease

**Medications:**
- Levothyroxine 50 mcg daily
- Ibuprofen 400 mg twice daily (started 2 weeks ago for joint pain)

**Social History:**
- Accountant
- Former smoker (quit 5 years ago; 10 pack-year history)
- Occasional alcohol use

**Family History:**
- Sister has "lupus"
- Mother has thyroid disease

### Physical Examination
- **Vital Signs:** BP 124/78 mmHg, HR 76 bpm, Temp 37.1C, BMI 26 kg/m2
- **General:** Appears fatigued, no acute distress
- **Hands:**
  - Bilateral synovitis of MCP joints 2-4 (boggy swelling, warmth)
  - Bilateral synovitis of wrist joints
  - PIP joints mildly swollen bilaterally
  - DIP joints normal
  - Reduced grip strength
  - No Heberden or Bouchard nodes
- **Feet:**
  - Tenderness and swelling at MTP joints 2-5 bilaterally
  - "Squeeze test" positive (transverse compression of MTP joints causes pain)
- **Elbows:** Small nodule palpated over right olecranon
- **Other joints:** No knee, ankle, or shoulder involvement

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| ESR | 52 mm/hr | 0-20 mm/hr |
| CRP | 3.8 mg/dL | <0.5 mg/dL |
| Rheumatoid Factor | 156 IU/mL | <14 IU/mL (positive) |
| Anti-CCP | >250 U/mL | <20 U/mL (strongly positive) |
| ANA | 1:40 (low titer) | <1:80 |
| CBC | Hgb 11.2 g/dL, normal WBC and platelets | Hgb 12-16 g/dL |
| Complete Metabolic Panel | Normal | - |
| Hepatitis B and C serologies | Negative | - |

**Imaging:**
- **Hand and wrist radiographs:**
  - Periarticular osteopenia at MCP and PIP joints
  - Soft tissue swelling
  - No definite erosions yet
- **Foot radiographs:**
  - Soft tissue swelling at MTP joints
  - Early marginal erosion at 5th MTP joint

### Clinical Image

![Rheumatoid arthritis hands](case_01_image.jpg)

*Clinical photograph of hands demonstrating symmetric swelling at the metacarpophalangeal and proximal interphalangeal joints with early ulnar deviation, characteristic of rheumatoid arthritis. Source: [Wikimedia Commons](https://commons.wikimedia.org/wiki/File:Rheumatoid_Arthritis.JPG), CC BY-SA 3.0.*

### Diagnosis
**Rheumatoid Arthritis (Seropositive)**

**2010 ACR/EULAR Classification Criteria Score:**
- Joint involvement (4-10 small joints): 3 points
- Serology (high-positive RF and high-positive anti-CCP): 3 points
- Acute phase reactants (elevated ESR and CRP): 1 point
- Duration (>6 weeks): 1 point
- **Total: 8 points (>=6 required for classification)**

**Poor Prognostic Factors Present:**
- High-positive RF and anti-CCP ("double positive")
- Elevated inflammatory markers
- Early radiographic erosion (5th MTP)
- Rheumatoid nodule
- Smoking history

### Treatment Plan

**Initial DMARD Therapy:**
1. **Methotrexate:** Start 15 mg PO weekly, titrate to 20-25 mg as tolerated
2. **Folic acid:** 1 mg daily to reduce methotrexate side effects
3. **Prednisone:** 10 mg daily as bridging therapy, taper over 8-12 weeks as methotrexate takes effect

**Monitoring:**
- CBC and CMP every 4-8 weeks during methotrexate initiation
- Hepatitis B/C screening completed (negative)
- Chest X-ray baseline (before methotrexate)

**Patient Education:**
- Avoid alcohol while on methotrexate
- Contraception counseling (methotrexate is teratogenic)
- Report signs of infection
- Smoking cessation counseling (improves treatment response)

**Follow-up:**
- Reassess disease activity (DAS28) in 8-12 weeks
- If inadequate response, consider adding biologic (TNF inhibitor or other) or switching to subcutaneous methotrexate
- Target: Remission (DAS28 <2.6) or low disease activity (<3.2)

### Teaching Points
1. **Early diagnosis is critical:** The "window of opportunity" for treatment within 3-6 months of symptom onset improves long-term outcomes
2. **Double seropositivity:** Patients positive for both RF and anti-CCP, particularly at high titers, have more aggressive erosive disease
3. **Treat-to-target:** Regular disease activity assessment with therapy adjustment to achieve remission or low disease activity
4. **Methotrexate as anchor:** First-line DMARD; folate supplementation reduces side effects without compromising efficacy
5. **Bridging therapy:** Short-term glucocorticoids provide rapid symptom relief while awaiting DMARD effect (takes weeks to months)

---

## Case 2: Established Rheumatoid Arthritis with Extra-Articular Manifestations

### Patient Presentation
**Demographics:** 58-year-old woman

**Chief Complaint:** "My RA has been flaring, and I've noticed increased shortness of breath."

**History of Present Illness:**
The patient has a 15-year history of seropositive rheumatoid arthritis, initially well-controlled on methotrexate but with increasing disease activity over the past year. She has developed multiple subcutaneous nodules on her elbows and fingers. Over the past 4 months, she has noticed progressive exertional dyspnea, now occurring with walking one block. She has a dry, nonproductive cough. She also reports dry eyes requiring frequent artificial tear use and dry mouth making it difficult to eat crackers without water.

**Past Medical History:**
- Rheumatoid arthritis diagnosed at age 43
- Hypertension
- Osteoporosis (steroid-induced)
- Secondary Sjogren syndrome

**Medications:**
- Methotrexate 20 mg weekly (on for 15 years)
- Folic acid 1 mg daily
- Prednisone 5 mg daily (unable to taper below this)
- Lisinopril 10 mg daily
- Alendronate 70 mg weekly
- Artificial tears as needed

**Social History:**
- Never smoker
- Retired librarian

### Physical Examination
- **Vital Signs:** BP 132/78 mmHg, HR 88 bpm, RR 18, SpO2 94% on room air, Temp 36.8C
- **General:** Appears chronically ill
- **Lungs:** Fine bibasilar crackles, no wheezes
- **Cardiovascular:** Regular rhythm, no murmurs
- **Hands:**
  - Ulnar deviation at MCP joints bilaterally
  - Swan neck deformity of bilateral 3rd and 4th fingers
  - Reduced grip strength
  - Multiple subcutaneous nodules on finger extensor surfaces
- **Elbows:** Large firm nodules over bilateral olecranons
- **Eyes:** Mild conjunctival injection
- **Mouth:** Reduced saliva pooling, mild tongue fissuring

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| ESR | 68 mm/hr | 0-20 mm/hr |
| CRP | 4.2 mg/dL | <0.5 mg/dL |
| RF | 384 IU/mL | <14 IU/mL |
| Anti-CCP | >340 U/mL | <20 U/mL |
| Anti-Ro (SSA) | Positive | Negative |
| Anti-La (SSB) | Positive | Negative |
| Hemoglobin | 10.8 g/dL | 12-16 g/dL |
| MCV | 88 fL | 80-100 fL |

**Pulmonary Function Tests:**
- FVC: 68% predicted (reduced)
- FEV1: 72% predicted
- FEV1/FVC: 0.82 (normal ratio)
- DLCO: 52% predicted (significantly reduced)
- Pattern consistent with restrictive lung disease

**Imaging:**
- **High-resolution CT chest:**
  - Bilateral reticular opacities, predominantly basilar
  - Ground-glass opacities
  - Traction bronchiectasis
  - Pattern consistent with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP)
- **Hand radiographs:**
  - Bilateral erosions at MCP and PIP joints
  - Joint space narrowing
  - Subluxation at multiple MCP joints

### Clinical Image

![Rheumatoid nodule histology](case_02_image.jpg)

*High magnification histology of a rheumatoid nodule showing central fibrinoid necrosis surrounded by palisading histiocytes (macrophages), characteristic of rheumatoid nodules. Source: [Wikimedia Commons](https://commons.wikimedia.org/wiki/File:Rheumatoid_nodule_-_high_mag.jpg), CC BY-SA 3.0.*

### Diagnosis
**Established Rheumatoid Arthritis with:**
1. **Rheumatoid interstitial lung disease** (ILD) - UIP or NSIP pattern
2. **Rheumatoid nodules** (multiple)
3. **Secondary Sjogren syndrome** (sicca symptoms with anti-Ro/La antibodies)
4. **Anemia of chronic disease**
5. **Joint deformities** (ulnar deviation, swan neck)

### Treatment Plan

**Address Interstitial Lung Disease:**
1. **Pulmonology referral** for further evaluation and co-management
2. **Consider mycophenolate mofetil:** May benefit both joints and ILD; methotrexate-associated pneumonitis must be excluded
3. **Discontinue methotrexate:** Concern for possible contribution to lung disease (though methotrexate pneumonitis is typically acute)
4. **Consider nintedanib:** Antifibrotic approved for progressive fibrosing ILD

**Modify RA Therapy:**
1. **Add rituximab:** B-cell depletion may benefit both RA and ILD, particularly with positive anti-Ro antibodies
2. **Continue low-dose prednisone:** May benefit both conditions
3. **Avoid JAK inhibitors:** Concern for VTE risk, and less data for ILD

**Manage Sicca Symptoms:**
1. Continue artificial tears, consider punctal plugs
2. Saliva substitutes, sipping water
3. Consider pilocarpine or cevimeline if inadequate

**Other Measures:**
1. Pneumococcal and influenza vaccination (if not up to date)
2. Continue osteoporosis treatment
3. Screen for depression (chronic disease burden)

### Teaching Points
1. **Pulmonary disease in RA:** ILD is a major cause of morbidity and mortality; screen with PFTs and HRCT when symptomatic; UIP pattern carries worse prognosis than NSIP
2. **Rheumatoid nodules:** Occur almost exclusively in RF-positive patients; paradoxically, methotrexate can cause accelerated nodulosis in some patients
3. **Secondary Sjogren syndrome:** Common overlap; sicca symptoms plus anti-Ro/La antibodies; increases lymphoma risk
4. **Treatment complexity:** ILD may require switching away from methotrexate; mycophenolate and rituximab have potential benefit for both joints and lungs
5. **Anemia of chronic disease:** Common in active RA; normocytic with low iron but elevated ferritin; responds to inflammation control rather than iron supplementation

---

## Case 3: Rheumatoid Arthritis Flare with Septic Joint Concern

### Patient Presentation
**Demographics:** 65-year-old man

**Chief Complaint:** "My left knee is extremely swollen and painful since yesterday."

**History of Present Illness:**
The patient has a 10-year history of seropositive rheumatoid arthritis, currently on adalimumab and methotrexate with reasonable disease control. He presents with acute onset of severe left knee pain and swelling that began approximately 18 hours ago. The knee is more painful than his typical RA flares. He has had difficulty bearing weight and low-grade fever (38.2C) at home. He had a dental cleaning one week ago. He denies other recent infections, trauma, or tick bites.

**Past Medical History:**
- Rheumatoid arthritis
- Type 2 diabetes mellitus
- Coronary artery disease with stent 3 years ago

**Medications:**
- Adalimumab 40 mg every 2 weeks (last dose 10 days ago)
- Methotrexate 20 mg weekly
- Folic acid 1 mg daily
- Metformin 1000 mg twice daily
- Aspirin 81 mg daily
- Atorvastatin 40 mg daily

**Social History:**
- Retired engineer
- Non-smoker

### Physical Examination
- **Vital Signs:** BP 142/88 mmHg, HR 102 bpm, Temp 38.4C, RR 18
- **General:** Uncomfortable, diaphoretic
- **Left Knee:**
  - Large tense effusion
  - Significant warmth and erythema
  - Exquisitely tender to palpation
  - Unable to flex or extend due to pain
  - Held in approximately 30 degrees of flexion
- **Other Joints:** Mild chronic synovitis at MCPs bilaterally, no acute inflammation

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| WBC | 14,200/mm3 | 4,500-11,000/mm3 |
| ESR | 88 mm/hr | 0-20 mm/hr |
| CRP | 18.2 mg/dL | <0.5 mg/dL |
| Blood Glucose | 245 mg/dL | 70-100 mg/dL |
| Creatinine | 1.1 mg/dL | 0.7-1.3 mg/dL |
| Blood Cultures | Pending | - |

**Synovial Fluid Analysis:**
| Test | Result | Interpretation |
|------|--------|----------------|
| Appearance | Cloudy, yellow | Inflammatory |
| WBC | 78,000/mm3 | Highly inflammatory (>50,000 suggests septic) |
| PMN | 92% | Neutrophil predominant |
| Crystals | None identified | Excludes crystal arthropathy |
| Gram Stain | Gram-positive cocci in clusters | Likely Staphylococcus |
| Culture | Pending | - |

**Imaging:**
- **Left knee X-ray:** Large effusion, chronic degenerative changes, no fracture

### Diagnosis
**Septic Arthritis of the Left Knee (presumed Staphylococcus aureus)**

**Risk Factors Present:**
- Immunosuppression (TNF inhibitor, methotrexate)
- Diabetes mellitus
- Pre-existing joint disease (RA)
- Recent dental procedure (potential source of bacteremia)

### Treatment Plan

**Emergent Management:**
1. **Orthopedic surgery consultation** for urgent arthroscopic lavage/debridement
2. **Hold adalimumab and methotrexate** - do not resume until infection cleared
3. **IV antibiotics:**
   - Empiric: Vancomycin 1.5g IV q12h (cover MRSA given immunosuppression and healthcare exposure)
   - Narrow based on culture results
4. **Serial knee aspirations** if surgery delayed; may need repeated drainage

**Supportive Care:**
1. IV fluids
2. Pain management (avoid NSAIDs given kidney considerations)
3. Diabetes management - insulin sliding scale while acutely ill

**Duration:**
- Minimum 4 weeks IV antibiotics for native joint septic arthritis
- May transition to oral if organism susceptible and good response

**Follow-up Considerations:**
1. Echocardiogram to rule out endocarditis (dental source, bacteremia)
2. Repeat synovial fluid analysis to confirm sterilization
3. Physical therapy once infection resolved
4. Discussion of RA therapy restart timing (typically 2-4 weeks after antibiotics completed)

### Teaching Points
1. **Septic arthritis in RA:** Patients on immunosuppression are at increased risk; must maintain high clinical suspicion even if presentation overlaps with RA flare
2. **TNF inhibitors and infection:** Increase risk of serious infections, particularly bacterial and mycobacterial; must be held during active infection
3. **Synovial WBC >50,000:** Strongly suggests septic arthritis; crystals should also be excluded as they can coexist
4. **Gram-positive cocci in clusters:** Likely Staphylococcus aureus, the most common cause of septic arthritis
5. **Urgent drainage:** Essential for joint preservation; delays of even 24-48 hours worsen outcomes and risk of permanent joint damage
6. **Pre-existing joint disease:** Damaged joints (RA, OA) are more susceptible to bacterial seeding during bacteremia; dental procedures, urinary tract infections, and skin infections are common sources