Scleroderma

Background

• Autoimmune collagen vascular disease, aka Systemic Sclerosis
• Inappropriate and excessive accumulation of collagen and matrix in various tissues
• Widespread vascular lesions
  • Endothelial dysfunction
  • Vascular spasm
  • Vascular wall thickening
  • Narrowed lumen
• Two types:
  • Diffuse Systemic Sclerosis: skin changes, which can progress to internal organ involvement
  • Limited Cutaneous Systemic Sclerosis, aka "CREST Syndrome"

Clinical Features

• Systemic complaints (fever, malaise, fatigue, weight loss, myalgias)
• Diffuse Systemic Sclerosis
  • hypo- or hyper- pigmentation of skin, extending from fingers and toes proximally, also involving chest and abdominal wall
  • Pigment is perserved around hair follicles leading to salt and pepper appearance
    

    Hypopigmentation in Diffuse Scleroderma, courtesy of Regional Derm website
  • Symmetric hand edema and Raynaud's phenomenon
  • Abrupt disease presentation; worse in first 18 months, then either improvement or worsening to involve internal organs
• CREST Syndrome
  • Longstanding Raynaud's
  • Skin thickening and fibrosis distal to elbows and knees, and on face
  • Subcutaneous calcinosis
  • Esophageal dysmotility
  • Sclerodactyly
  • Telangiectasia
  • Indolent course

Emergencies

• Renal crisis
  • Causes are vessel narrowing and subsequent ischemic kidney disease
  • Leads to hypertensive emergency, acute renal failure, and microangiopathic hemolytic anemia
  • Occurs during first 5 years of the disease
    • Was the most common cause of death prior to ACEi usage
  • Severe renal crisis is life threatening with incidence of 8-10% in Limited and 10-20% in diffuse
    • Similar to TTP/HUS with microangiography
    • Poor prognosis with sudden onset of hypertension, encephalopathy, CVA, retinopathy
    • Risk factors are rapidly progressing diffuse scleroderma, high dose glucocorticoid use, cyclosporine therapy, presence of anti-RNA-polymerase antibodies.
• Pulmonary
  • Respiratory failure
  • Interstitial lung disease, leading to pulmonary fibrosis
    • Found in dorsal portion of both lower lobes, but can extend to upper lobes in severe diease
    • Poor prognosis with severe pulmonary impairment. 42% die within 10 years of disease onset
  • ARDS
  • Aspiration pneumonitis
  • Pulmonary hypertension
    • Gradually progressive exercise breathlessness
    • Fatigue
    • Hoarseness from nerve palsy caused by dilated pulmonary artery stem
  • Alveolar hemorrhage
    • Hemoptysis, infiltrates on CXR, anemia.
• Cardiac
  • Acute heart failure
    • Can be from diastolic dysfunction, malignant hypertension during renal crisis, and decompensated pulmonary hypertension
  • Cardiopulmonary complications are the most common causes of scleroderma-related death, with cardiac causes and pulmonary fibrosis being the most common.
  • Anginal pain from right ventricle ischemia and low cardiac output

Differential Diagnosis

• Systemic Lupus Erythematosus
• Sjögren syndrome

Blue Digit

• Acute arterial ischemia
  • Atheroembolism (AKA Blue Toe Syndrome)
  • Arterial embolism
  • Arterial thrombosis
• Vasospastic Disorders
  • Raynaud’s disease
  • Primary erythromelalgia
• Autoimmune
  • Scleroderma
  • SLE
• Idiopathic
  • Thromboangiitis obliterans (Buerger's disease)
• Chronic peripheral artery disease
  • Atherosclerosis obliterans

Evaluation

• Frequent blood pressure checks
• Serologic markers for each subset
• UA for proteinuria or hematuria
• BMP
• CXR, CT chest
• +/- echo, right heart cath, lung biopsy
• CREST syndrome
  • May need endoscopy and Hemoccult test to evaluate for blood loss from mucosal telangiectasias (gastric antral vascular ectasia, described as "watermelon stomach."

Management

Renal crisis

• Rapid control of blood pressure
  • ACEI drug of choice, e.g. captopril 6.25 to 12.5mg PO, TID.
• Avoid diuretics
  • Consult renal, as 50% of patients will require dialysis.

Pulmonary hypertension

• Chronic management may include prostaglandin derivatives (e.g. epoprostenol), PDE-5 inhibitors (e.g. sildenafil), and/or endothelin receptor antagonists (e.g. bosentan)
• Acute decompensation:
  • Optimize (usually reduce) RV preload:
    • Usually euvolemic or hypervolemic, rarely need IV fluids so diuretics can benefit and treat the RV failure
    • Furosemide 20-40mg IV or drip at 5-20 mg/hr
    • If suspect sepsis or hypovolemia, small (250-500cc) NS challenge to assess fluid responsiveness. If not responsive to IVF challenge, start norepinephrine (MAP > 65 mmHg).
  • Increase cardiac output
    • Once MAP >65 mmHg, start low dose dobutamine (5-10mcg/kg/min)
    • Improves inotropic support and theoretically decreases pulmonary vascular resistance
  • Reduce RV afterload
    • Avoid hypoxia, maintain O2 sat >90% (increases pulmonary vasoconstriction)
    • Avoid hypercapnia (increases pulmonary vascular resistance)
    • Avoid acidosis
  • Treat arrhythmias:
    • Avoid calcium channel blockers and β-blockers
  • Optimize oxygenation
    • Intubated patients should be optimized to increased O2 delivery and minimize hypercapnia, maintain low tidal volumes and low PEEP as tolerated

Interstitial lung disease

• Steroids
• Cyclophosphamide
• Ventilatory support prn

Alveolar hemorrhage

• Airway stabilization if large volume hemoptysis or problems with oxygenation/ventilation (>8.0 ETT preferable)
• IV corticosteroids - high dose Methylprednisolone Q6H or cyclophosphamide
• Bronchoscopy for vessel localization
• Vessel embolization if localizable
• Management of Hemoptysis
  • Hemoptysis, infiltrates on CXR, anemia.
  • Emergent bronchoscopy
  • High dose corticosteroids, cyclophosphamide, local vessel embolization or plasma exchange

CREST Syndrome

• Empiric treatment with a PPI to prevent reflux and stricture formation
• Transfuse as needed for anemia due to mucosal telangiectasias
• Ursodiol treatment if concomitant primary biliary cirrhosis to prevent progression to secondary cirrhosis

Disposition

• Hospitalization for any elevation in blood pressure, difficulty breathing, evidence of heart strain or pulmonary edema.

See Also

• Collagen vascular disease