# Clinical Cases: Autoimmunity

## Case 1: Systemic Lupus Erythematosus

### Patient Demographics
- **Age:** 28 years old
- **Sex:** Female
- **Ethnicity:** African American

### Chief Complaint
Joint pain, facial rash, and fatigue for 3 months

### History of Present Illness
A 28-year-old woman presents with a 3-month history of progressive fatigue, joint pain, and a rash on her face. She describes morning stiffness lasting over an hour and symmetric pain in her hands, wrists, and knees without significant swelling. The facial rash appeared after sun exposure during a beach vacation and has persisted. She also reports hair loss, oral ulcers, and occasional low-grade fevers. Recently, she noticed swelling in her legs and foamy urine.

### Past Medical History
- Recurrent episodes of pleuritic chest pain over past year
- History of photosensitivity
- One miscarriage at 12 weeks gestation

### Family History
- Mother with rheumatoid arthritis
- Maternal aunt with Sjogren's syndrome

### Physical Examination
- **General:** Fatigued-appearing woman in no acute distress
- **Vital Signs:** T 37.8C, HR 92, RR 16, BP 148/94
- **Skin:** Erythematous malar rash sparing nasolabial folds; diffuse alopecia; oral ulcers on hard palate
- **Musculoskeletal:** Tenderness at MCPs, wrists, and knees bilaterally without synovitis
- **Cardiovascular:** Normal S1/S2, no murmurs or rubs
- **Pulmonary:** Decreased breath sounds at left base
- **Extremities:** 2+ pitting edema to mid-calf bilaterally

### Laboratory Workup
| Test | Result | Reference Range |
|------|--------|-----------------|
| WBC | 3,100/uL | 4,500-11,000/uL |
| Hemoglobin | 10.2 g/dL | 12-16 g/dL |
| Platelets | 98,000/uL | 150,000-400,000/uL |
| Creatinine | 1.4 mg/dL | 0.6-1.2 mg/dL |
| **ANA** | **1:640 homogeneous** | Negative |
| **Anti-dsDNA** | **Positive (high titer)** | Negative |
| **Anti-Smith** | **Positive** | Negative |
| Complement C3 | 45 mg/dL (low) | 90-180 mg/dL |
| Complement C4 | 8 mg/dL (low) | 10-40 mg/dL |
| Urinalysis | 3+ protein, 2+ blood, RBC casts | Normal |
| 24-hour urine protein | 3.2 g | <150 mg |
| Chest X-ray | Small left pleural effusion | Normal |

### Clinical Image
![Malar Rash Pattern](case_01_image.jpg)

*Image showing characteristic malar (butterfly) rash distribution pattern seen in systemic lupus erythematosus, typically sparing the nasolabial folds. Image source: Course lecture materials.*

### Diagnosis
**Systemic Lupus Erythematosus (SLE) with Class IV Lupus Nephritis**

### Discussion
SLE is a prototypical systemic autoimmune disease characterized by autoantibodies against nuclear antigens and multi-organ involvement:

**Pathogenesis:**
- Defective clearance of apoptotic cells exposes nuclear antigens
- Loss of tolerance leads to autoantibody production (ANA, anti-dsDNA, anti-Smith)
- Immune complex deposition causes inflammation via complement activation
- Type I interferon signature amplifies the autoimmune response

**This patient meets multiple classification criteria:**
- Malar rash (photosensitive)
- Arthritis (non-erosive)
- Serositis (pleuritis)
- Renal involvement (nephritis with proteinuria and casts)
- Hematologic (leukopenia, anemia, thrombocytopenia)
- ANA positive
- Anti-dsDNA and anti-Smith positive

**Autoantibodies in SLE and their associations:**
| Autoantibody | Association |
|--------------|-------------|
| Anti-dsDNA | Lupus nephritis, disease activity |
| Anti-Smith | Most specific for SLE |
| Anti-Ro (SS-A) | Neonatal lupus, photosensitivity |
| Anti-La (SS-B) | Sjogren's overlap |
| Antiphospholipid | Thrombosis, pregnancy loss |

**Low complement levels indicate active immune complex disease.**

### Treatment
1. **Immediate:** Renal biopsy to classify nephritis
2. **Induction therapy:** Mycophenolate mofetil or cyclophosphamide plus corticosteroids for Class IV nephritis
3. **Maintenance:** Mycophenolate mofetil with low-dose prednisone
4. **Hydroxychloroquine:** All SLE patients (reduces flares, thrombosis, damage accrual)
5. **Sun protection:** Strict photoprotection
6. **Monitoring:** Anti-dsDNA titers and complement levels correlate with disease activity

---

## Case 2: Rheumatoid Arthritis

### Patient Demographics
- **Age:** 45 years old
- **Sex:** Female
- **Ethnicity:** Caucasian

### Chief Complaint
Painful, swollen joints in hands for 6 months

### History of Present Illness
A 45-year-old woman presents with a 6-month history of joint pain and swelling primarily affecting her hands. She reports morning stiffness lasting 2-3 hours that improves with activity. The symptoms began insidiously, first affecting her fingers, and have progressively involved her wrists and feet. She has noticed difficulty making a fist and has had to remove her rings due to finger swelling. She also reports fatigue and a 5-pound unintentional weight loss.

### Past Medical History
- 20-pack-year smoking history (quit 5 years ago)
- No prior joint problems

### Family History
- Sister with rheumatoid arthritis
- Mother with hypothyroidism

### Physical Examination
- **General:** Well-appearing woman with obvious hand deformities
- **Vital Signs:** Normal
- **Hands:** Symmetric swelling and tenderness of MCPs (2nd-5th bilaterally) and PIPs; warmth over affected joints; boggy synovium on palpation; decreased grip strength
- **Wrists:** Bilateral swelling and tenderness with limited extension
- **Feet:** Tenderness at MTPs bilaterally (squeeze test positive)
- **No subcutaneous nodules palpated**

### Laboratory Workup
| Test | Result | Reference Range |
|------|--------|-----------------|
| ESR | 58 mm/hr | 0-20 mm/hr |
| CRP | 3.8 mg/dL | <0.5 mg/dL |
| **Rheumatoid Factor** | **186 IU/mL** | <14 IU/mL |
| **Anti-CCP antibody** | **>250 U/mL** | <20 U/mL |
| ANA | 1:80 (speckled) | Negative |
| CBC | Normal | -- |
| Hand X-rays | Periarticular osteopenia, joint space narrowing MCPs, early erosions at 2nd and 3rd MCP | Normal |

### Diagnosis
**Seropositive Rheumatoid Arthritis** with early erosive disease

### Discussion
Rheumatoid arthritis is a chronic inflammatory joint disease characterized by symmetric polyarthritis with progressive joint destruction:

**Pathogenesis:**
- Genetic susceptibility: HLA-DR4 "shared epitope" association
- Environmental trigger: Smoking promotes citrullination of proteins
- Autoimmunity: Anti-CCP antibodies target citrullinated proteins
- Synovial inflammation: T cells, B cells, macrophages produce TNF-alpha, IL-1, IL-6
- Pannus formation: Proliferating synovium invades and destroys cartilage and bone

**Why is anti-CCP important?**
- More specific for RA than rheumatoid factor (95% vs 70%)
- Predicts erosive disease and worse prognosis
- Can be positive years before clinical disease onset
- Helps distinguish RA from other causes of RF positivity

**Joint involvement pattern in RA:**
- **Affected:** MCPs, PIPs, wrists, MTPs (symmetric)
- **Spared:** DIPs (unlike osteoarthritis and psoriatic arthritis)

**Extra-articular manifestations (not yet present):**
- Rheumatoid nodules (elbows, lungs)
- Interstitial lung disease
- Felty syndrome (splenomegaly, neutropenia)
- Cardiovascular disease (accelerated atherosclerosis)

### Treatment
1. **Early aggressive treatment:** Treat-to-target strategy (low disease activity or remission)
2. **Conventional DMARDs:** Methotrexate first-line (anchor drug)
3. **Biologic DMARDs if inadequate response:**
   - TNF inhibitors (adalimumab, etanercept)
   - Other options: Abatacept (costimulation blockade), Rituximab (B cell depletion), JAK inhibitors
4. **Bridging therapy:** Low-dose prednisone while DMARDs take effect
5. **Monitoring:** Disease activity scores, inflammatory markers, imaging for erosion progression
6. **Cardiovascular risk management:** Aggressive risk factor modification

---

## Case 3: Myasthenia Gravis

### Patient Demographics
- **Age:** 32 years old
- **Sex:** Female
- **Ethnicity:** Asian

### Chief Complaint
Double vision and difficulty chewing for 2 months

### History of Present Illness
A 32-year-old woman presents with intermittent double vision (diplopia) and difficulty chewing tough foods that has progressed over 2 months. She first noticed drooping of her eyelids (ptosis) in the evening after long days at work, which initially improved after rest. Over time, she developed horizontal diplopia and her jaw feels "tired" after eating. She denies limb weakness, difficulty breathing, or swallowing problems. Symptoms consistently worsen throughout the day and improve after rest.

### Past Medical History
- Graves disease diagnosed 3 years ago (treated with radioiodine ablation)
- Currently on levothyroxine

### Physical Examination
- **General:** Alert woman, appears comfortable
- **Vital Signs:** Normal
- **HEENT:** Bilateral ptosis, worse on right; positive fatigue test (ptosis worsens with sustained upgaze); diplopia on lateral gaze
- **Cranial nerves:** Otherwise intact; no facial weakness; voice normal
- **Neck:** Well-healed thyroidectomy scar
- **Motor:** 5/5 strength in all extremities; no fatigability with repetitive testing
- **Sensory:** Intact
- **Reflexes:** 2+ throughout, symmetric

### Diagnostic Testing
| Test | Result | Reference Range |
|------|--------|-----------------|
| **Acetylcholine receptor antibodies** | **18.5 nmol/L** | <0.4 nmol/L |
| Anti-MuSK antibodies | Negative | Negative |
| TSH | 2.1 mIU/L | 0.4-4.0 mIU/L |
| Repetitive nerve stimulation | >10% decrement | <10% decrement |
| CT chest | 3 cm anterior mediastinal mass | Normal |

### Diagnosis
**Myasthenia Gravis (MG)** with thymoma, ocular-predominant with bulbar involvement

### Discussion
Myasthenia gravis is an antibody-mediated autoimmune disorder targeting the neuromuscular junction:

**Immunopathogenesis:**
- Anti-AChR antibodies (present in 85% of generalized MG) cause:
  - Accelerated receptor internalization and degradation
  - Complement-mediated destruction of postsynaptic membrane
  - Direct blockade of acetylcholine binding
- Anti-MuSK antibodies (5-8%) cause impaired AChR clustering
- Results in reduced safety factor at neuromuscular junction

**This patient demonstrates classic features:**
- **Fatigable weakness:** Worse with use, improves with rest
- **Diurnal variation:** Worse as day progresses
- **Preferential ocular/bulbar involvement:** Ptosis, diplopia, jaw fatigue
- **Association with other autoimmune disease:** Graves disease

**Thymoma and MG:**
- Thymic abnormalities in 75% of MG patients
- Thymoma in 10-15% (requires surgical resection)
- Thymic hyperplasia in 60-65%
- Thymectomy improves outcomes even without thymoma

**MG classification by affected muscle groups:**
| Class | Description |
|-------|-------------|
| I | Ocular only |
| II | Mild generalized |
| III | Moderate generalized |
| IV | Severe generalized |
| V | Requiring intubation |

### Treatment
1. **Symptomatic:** Pyridostigmine (acetylcholinesterase inhibitor)
2. **Immunosuppression:** Prednisone, azathioprine, or mycophenolate for generalized disease
3. **Thymectomy:** Indicated for thymoma (mandatory) and non-thymoma MG under age 65
4. **Crisis management:** IVIG or plasmapheresis for myasthenic crisis
5. **Monitor for respiratory compromise:** Forced vital capacity
6. **Avoid medications that worsen MG:** Aminoglycosides, beta-blockers, quinolones, magnesium

**Myasthenic crisis warning signs:** Dyspnea, weak cough, difficulty swallowing secretions