# Clinical Cases: Connective Tissue Diseases

## Case 1: Systemic Lupus Erythematosus with Nephritis

### Patient Presentation
**Demographics:** 28-year-old African American woman

**Chief Complaint:** "I have a rash on my face, my joints hurt, and my legs are swelling."

**History of Present Illness:**
The patient presents with a 6-week history of progressive symptoms including a facial rash that worsens with sun exposure, painful swelling in her hands and knees, fatigue, and bilateral leg swelling that leaves indentations when pressed. She also reports intermittent fevers, hair loss (finding clumps in her hairbrush), and mouth sores that are mostly painless. She noticed her urine has been "foamy" for the past two weeks. She denies any history of similar symptoms.

**Past Medical History:**
- No significant prior medical history
- Two previous first-trimester miscarriages

**Medications:**
- Prenatal vitamins (not currently pregnant)
- Ibuprofen occasionally for headaches

**Family History:**
- Maternal aunt has "lupus"
- Mother has hypothyroidism

**Social History:**
- Works as a marketing executive
- Non-smoker
- Social alcohol use

### Physical Examination
- **Vital Signs:** BP 152/98 mmHg, HR 92 bpm, Temp 37.8C, BMI 24 kg/m2
- **Skin:**
  - Erythematous malar rash across cheeks and nasal bridge, sparing nasolabial folds
  - Diffuse non-scarring alopecia
- **Oral:** Painless ulcers on hard palate
- **Cardiovascular:** Distant friction rub heard at left sternal border
- **Lungs:** Decreased breath sounds at left base
- **Extremities:**
  - Bilateral pitting edema to mid-shins
  - Synovitis at bilateral MCPs, PIPs, and wrists (non-erosive pattern)
- **Neurologic:** Normal

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| ANA | 1:640, homogeneous pattern | <1:80 |
| Anti-dsDNA | 320 IU/mL | <30 IU/mL (strongly positive) |
| Anti-Smith | Positive | Negative |
| C3 | 45 mg/dL | 90-180 mg/dL (low) |
| C4 | 8 mg/dL | 16-47 mg/dL (low) |
| ESR | 78 mm/hr | 0-20 mm/hr |
| CRP | 1.2 mg/dL | <0.5 mg/dL |
| Creatinine | 1.4 mg/dL | 0.6-1.2 mg/dL |
| Urinalysis | Protein 3+, RBC 50/hpf, RBC casts | Normal |
| 24-hour urine protein | 3.8 g/day | <150 mg/day |
| Hemoglobin | 9.8 g/dL | 12-16 g/dL |
| WBC | 3,200/mm3 | 4,500-11,000/mm3 |
| Platelets | 98,000/mm3 | 150,000-400,000/mm3 |
| Direct Coombs | Positive | Negative |
| Antiphospholipid antibodies | Anticardiolipin IgG positive | Negative |

**Imaging:**
- **Chest X-ray:** Small left pleural effusion, cardiomegaly
- **Echocardiogram:** Small pericardial effusion, normal EF

**Renal Biopsy:**
- Class IV diffuse proliferative lupus nephritis
- Active lesions with cellular crescents
- Activity index 12/24, Chronicity index 2/12

### Clinical Image

![Lupus malar rash](case_01_image.jpg)

*Clinical photograph demonstrating the characteristic malar (butterfly) rash of systemic lupus erythematosus, with erythema over the cheeks and nasal bridge sparing the nasolabial folds. Source: [Wikimedia Commons](https://commons.wikimedia.org/wiki/File:Lupusfoto.jpg), Public Domain.*

### Diagnosis
**Systemic Lupus Erythematosus with Class IV Lupus Nephritis**

**2019 EULAR/ACR Criteria (Score >=10 required):**
- Malar rash: 6 points
- Oral ulcers: 2 points
- Arthritis: 6 points
- Serositis (pericarditis, pleuritis): 5 points
- Renal (Class IV nephritis with proteinuria): 10 points
- Leukopenia: 3 points
- Thrombocytopenia: 4 points
- Hemolytic anemia (positive Coombs): 4 points
- Anti-dsDNA (high titer): 6 points
- Anti-Smith: 6 points
- Low complement: 3 points
- **Total: >10 points - criteria met**

### Treatment Plan

**Induction Therapy for Class IV Lupus Nephritis:**
1. **Mycophenolate mofetil:** 1g PO BID, titrate to 1.5g BID
2. **Methylprednisolone:** 1g IV daily x 3 days (pulse), then prednisone 1 mg/kg/day with taper
3. **Hydroxychloroquine:** 200 mg PO BID (all lupus patients unless contraindicated)

**Supportive Care:**
1. **ACE inhibitor:** Lisinopril 10 mg daily (renal protection, blood pressure)
2. **Sun protection:** SPF 30+ daily, sun avoidance
3. **Bone protection:** Calcium and vitamin D supplementation
4. **Aspirin:** 81 mg daily (given positive antiphospholipid antibodies)

**Monitoring:**
- Urinalysis and creatinine every 2-4 weeks initially
- Anti-dsDNA and complement levels to track activity
- Complete blood counts monthly

**Patient Education:**
- Pregnancy should be avoided during active nephritis and on mycophenolate (teratogenic)
- Contraception counseling
- Sun exposure worsens disease

### Teaching Points
1. **SLE demographics:** Predominantly affects women of childbearing age; African Americans, Hispanics, and Asians have higher incidence and often more severe disease
2. **Anti-dsDNA and complement:** Rising anti-dsDNA and falling complement often herald disease flares, particularly nephritis
3. **Lupus nephritis classification:** Class IV (diffuse proliferative) is the most severe and requires aggressive immunosuppression; biopsy guides therapy
4. **Hydroxychloroquine:** Foundation of SLE therapy; reduces flares, improves survival, and provides cardiovascular protection
5. **CRP in lupus:** Paradoxically, CRP is often normal or minimally elevated in SLE flares unless serositis or infection is present (ESR is typically elevated)

---

## Case 2: Diffuse Cutaneous Systemic Sclerosis with Renal Crisis

### Patient Presentation
**Demographics:** 52-year-old Caucasian woman

**Chief Complaint:** "My skin has been getting tight all over, and now I have a terrible headache and my vision is blurry."

**History of Present Illness:**
The patient was diagnosed with systemic sclerosis 18 months ago when she developed Raynaud phenomenon and skin thickening of her fingers. Over the past year, her skin tightening has progressed to involve her arms, chest, and face. She has had worsening gastroesophageal reflux and difficulty swallowing solids. She was recently started on prednisone 25 mg daily by her rheumatologist for progressive skin disease. She now presents with acute onset of severe headache, blurred vision, and malaise beginning 24 hours ago.

**Past Medical History:**
- Systemic sclerosis (diffuse cutaneous) diagnosed 18 months ago
- Raynaud phenomenon
- GERD
- No prior hypertension

**Medications:**
- Prednisone 25 mg daily (started 3 weeks ago)
- Omeprazole 40 mg twice daily
- Nifedipine 30 mg daily for Raynaud

**Allergies:** NKDA

### Physical Examination
- **Vital Signs:** BP 218/134 mmHg, HR 108 bpm, RR 22, Temp 36.9C
- **General:** Appears ill, anxious
- **HEENT:** Retinal hemorrhages and exudates on fundoscopy (hypertensive retinopathy)
- **Skin:**
  - Diffuse skin thickening involving fingers, hands, forearms, upper arms, face, and anterior chest
  - Sclerodactyly with tapered fingers
  - Digital pitting scars
  - Telangiectasias on face and hands
  - Skin score 32/51 (modified Rodnan skin score)
- **Cardiovascular:** Tachycardia, regular rhythm, S4 gallop
- **Lungs:** Clear to auscultation
- **Abdomen:** Non-tender

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| Creatinine | 4.2 mg/dL | 0.6-1.2 mg/dL (baseline 0.9 mg/dL) |
| BUN | 68 mg/dL | 7-20 mg/dL |
| Hemoglobin | 8.4 g/dL | 12-16 g/dL |
| Platelets | 72,000/mm3 | 150,000-400,000/mm3 |
| LDH | 780 U/L | 140-280 U/L |
| Haptoglobin | <10 mg/dL | 30-200 mg/dL |
| Reticulocyte count | 4.8% | 0.5-2.5% |
| Peripheral smear | Schistocytes present | None |
| ANA | 1:320 | <1:80 |
| Anti-Scl-70 | Negative | Negative |
| Anti-RNA polymerase III | Positive | Negative |
| Urinalysis | Protein 2+, RBC 25/hpf | Normal |

**Imaging:**
- **Chest X-ray:** Normal cardiac silhouette
- **Renal Ultrasound:** Normal-sized kidneys without obstruction

### Clinical Image

![Sclerodactyly](case_02_image.jpg)

*Clinical photograph demonstrating sclerodactyly in systemic sclerosis with tight, shiny skin of the fingers, tapered digits, and flexion contractures. Source: [Wikimedia Commons](https://commons.wikimedia.org/wiki/File:Sclerodactyly_in_progressive_systemic_sclerosis.jpg), CC BY-SA 4.0.*

### Diagnosis
**Scleroderma Renal Crisis with Microangiopathic Hemolytic Anemia**

**Diagnostic Features:**
- New-onset severe hypertension (previously normotensive)
- Rapidly progressive acute kidney injury
- Microangiopathic hemolytic anemia (schistocytes, elevated LDH, low haptoglobin)
- Thrombocytopenia
- Diffuse cutaneous systemic sclerosis within first 4 years
- Positive anti-RNA polymerase III antibodies (strongly associated with renal crisis)
- Recent high-dose corticosteroid use (precipitating factor)

### Treatment Plan

**Emergent Management:**
1. **ACE inhibitor - CRITICAL:** Captopril 6.25 mg initially, titrate rapidly to control BP
   - ACE inhibitors are lifesaving in scleroderma renal crisis
   - Continue even if creatinine rises initially
   - Target BP <140/90 within 72 hours
2. **Admit to ICU** for close monitoring
3. **Discontinue prednisone** - steroids may have precipitated crisis
4. **Prepare for possible dialysis** - may be needed temporarily

**Blood Pressure Management:**
- ACE inhibitors are first-line and should not be discontinued
- Add additional agents (calcium channel blockers) if needed
- Avoid beta-blockers initially (may worsen Raynaud)

**Monitoring:**
- Hourly blood pressure initially
- Daily creatinine, LDH, hemoglobin, platelets
- Urine output

**Prognosis Discussion:**
- 1-year survival has improved to ~80% with ACE inhibitors (was <15% before)
- ~50% may require temporary dialysis
- ~20-30% may recover renal function and come off dialysis

### Teaching Points
1. **Scleroderma renal crisis:** Medical emergency characterized by acute hypertension and AKI; occurs predominantly in early diffuse disease
2. **Anti-RNA polymerase III antibodies:** Strongly associated with renal crisis (and malignancy); presence should heighten vigilance
3. **Corticosteroids as trigger:** Doses >15 mg prednisone/day increase risk of renal crisis; avoid high-dose steroids in diffuse scleroderma
4. **ACE inhibitors are critical:** Continue even if creatinine rises; they have transformed outcomes in this previously fatal complication
5. **Microangiopathic hemolytic anemia:** Schistocytes, elevated LDH, low haptoglobin, thrombocytopenia - results from endothelial damage in renal vasculature

---

## Case 3: Dermatomyositis with Occult Malignancy

### Patient Presentation
**Demographics:** 62-year-old woman

**Chief Complaint:** "I have a rash on my face and hands, and I'm having trouble getting out of chairs and climbing stairs."

**History of Present Illness:**
The patient describes 3 months of progressive weakness affecting her thighs and upper arms, making it difficult to rise from a seated position, climb stairs, and lift objects overhead. She has noticed a purple discoloration around her eyes and a rash on her hands that appeared around the same time. She reports a 15-pound unintentional weight loss over this period. She has also developed difficulty swallowing solid foods and occasionally chokes on liquids.

**Past Medical History:**
- Hypertension
- Hyperlipidemia
- No prior autoimmune disease

**Medications:**
- Amlodipine 5 mg daily
- Atorvastatin 20 mg daily (on for 3 years without issue)

**Social History:**
- Retired accountant
- Never smoker
- No alcohol

**Family History:**
- Mother had ovarian cancer at age 65

### Physical Examination
- **Vital Signs:** BP 138/82 mmHg, HR 78 bpm, Temp 37.0C, BMI 22 kg/m2
- **Skin:**
  - Heliotrope rash: violaceous erythema of the eyelids with periorbital edema
  - Gottron papules: erythematous-to-violaceous papules over MCP and PIP joints dorsal surfaces
  - V-sign: erythema over anterior neck and chest
  - Shawl sign: erythema over posterior shoulders and upper back
  - Periungual erythema with dilated capillary loops
- **Musculoskeletal:**
  - Proximal muscle weakness (4/5 strength in deltoids, hip flexors)
  - Difficulty rising from chair without using arms
  - No muscle tenderness
- **Neurologic:** Normal sensation, normal reflexes

### Workup and Results

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| CK | 4,850 U/L | 30-200 U/L (markedly elevated) |
| Aldolase | 28 U/L | 1.0-7.5 U/L (elevated) |
| AST | 186 U/L | 10-40 U/L |
| ALT | 124 U/L | 7-56 U/L |
| LDH | 520 U/L | 140-280 U/L |
| ESR | 42 mm/hr | 0-20 mm/hr |
| ANA | 1:320 | <1:80 |
| Anti-Mi-2 | Negative | Negative |
| Anti-TIF1-gamma | Positive | Negative |
| Anti-Jo-1 | Negative | Negative |

**EMG:** Myopathic pattern with fibrillation potentials, positive sharp waves, early recruitment

**MRI Thighs:** Bilateral symmetric edema in proximal thigh musculature (quadriceps, adductors) consistent with active myositis

**Muscle Biopsy:** Perifascicular atrophy, perivascular inflammation with CD4+ T cells, complement deposition on capillaries - consistent with dermatomyositis

**Malignancy Screening (given age and anti-TIF1-gamma positivity):**
- **CT chest/abdomen/pelvis:** 3.5 cm ovarian mass, ascites
- **CA-125:** 485 U/mL (elevated)
- **PET scan:** Hypermetabolic ovarian mass with omental nodularity
- **Gynecologic oncology consultation:** Biopsy confirmed high-grade serous ovarian carcinoma

### Clinical Image

![Gottron papules](case_03_image.jpg)

*Clinical photograph showing Gottron papules - erythematous to violaceous papules over the dorsal aspects of the finger joints, a pathognomonic finding in dermatomyositis. Source: [Wikimedia Commons](https://commons.wikimedia.org/wiki/File:Dermatomyositis1.jpg), CC BY-SA 3.0.*

### Diagnosis
**Dermatomyositis Associated with Ovarian Carcinoma (Paraneoplastic)**

**Supporting Features:**
- Classic dermatomyositis rash (heliotrope, Gottron papules, V-sign, shawl sign)
- Proximal muscle weakness
- Markedly elevated CK
- Myopathic EMG
- MRI showing muscle edema
- Muscle biopsy consistent with dermatomyositis
- Anti-TIF1-gamma positive (strongly associated with malignancy)
- Ovarian carcinoma diagnosed on workup

### Treatment Plan

**Oncologic Management (Primary):**
1. **Gynecologic oncology referral** for staging and treatment of ovarian cancer
2. **Debulking surgery** planned
3. **Chemotherapy** (platinum-based) following surgery
4. Myositis may improve with cancer treatment

**Myositis Management:**
1. **Prednisone:** 1 mg/kg/day initially (coordinate with oncology regarding surgery timing)
2. **Consider IVIG:** May be added if inadequate response or if steroids problematic
3. **Dysphagia management:** Speech therapy evaluation, modified diet, aspiration precautions
4. **Physical therapy:** Maintain range of motion, gentle strengthening once inflammation controlled

**Monitoring:**
- CK levels to assess myositis response
- Repeat muscle strength assessment
- Monitor for aspiration pneumonia risk

**Prognosis:**
- Cancer-associated myositis may improve dramatically with effective cancer treatment
- Close coordination between rheumatology and oncology essential

### Teaching Points
1. **Dermatomyositis and malignancy:** Adult DM carries 3-8 fold increased cancer risk; most common within 3 years of myositis diagnosis
2. **Anti-TIF1-gamma antibodies:** Strongly associated with malignancy in adult dermatomyositis; presence mandates thorough cancer screening
3. **Malignancy screening:** Age-appropriate screening plus CT chest/abdomen/pelvis; ovarian cancer (women) and lung cancer (both sexes) are among the most common
4. **Characteristic skin findings:** Heliotrope rash (pathognomonic periorbital violaceous discoloration) and Gottron papules (over dorsal finger joints) are highly specific
5. **Paraneoplastic myositis:** May improve or resolve with successful cancer treatment; sometimes the myositis responds better to cancer therapy than to immunosuppression alone
6. **Dysphagia:** Common and dangerous complication; pharyngeal and esophageal muscle involvement creates aspiration risk