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 and Limited
  • 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 improvement or worsening to involve internal organs
• Liminted Sytemic Sclerosis, aka "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
  • Lead to hypertensive emergency, acute renal failure, and microangiopathic hemolytic anemia
  • Occurs during first 5 years of the disease
  • Treatment is strict BP control - ACEI drug of choice
    • 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, cyclosporin 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
    • Anginal pain from right ventricle ischemia and low cardiac output
    • Hoarseness from nerve palsy caused by dilated pulmonary artery stem
  • Alveolar hemorrhage
    • Hemoptysis, infiltrates on CXR, anemia.
    • Emergent bronchoscopy
    • High dose corticosteroids, cyclophosphamide, local vessel embolization or plasma exchange
• 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.

Differential Diagnosis

• Systemic Lupus Erythematous
• Sjogren's Syndrome
• Raynaud's Syndrome

Evaluation

• Frequent blood pressure checks
• Serologic markers for each subset
• Renal Crisis
  • Urinalysis for proteinuria or hematuria
  • Basic Metabolic Panel
  • Chest Xray for pulmonary edema
• Pulmonary Arterial Hypertension
  • Basic labs, including troponin
  • Echo to evaluate right heart and estimation of right atrial pressure
  • Right heart catheterization indicated in symptomatic patients
• Interstitial Lung Diease
  • Frequent checks of FVC to monitor disease
  • Chest xray, CT of the chest
  • Lung biopsy
• CREST Syndrome
  • 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
  • Start on ACE Inhibitor, captopril 6.25 to 12.5mg PO, TID.
  • Avoid diuretics
  • Consult Nephrology, as 50% of patients will require dialysis.
• Pulmonary Arterial Hypertension
  • Warfarin to prevent Pulmonary Embolism
  • Endothelin-I receptor antagonist, phosphodiesterase inhibitor or IV prostanoids
• Interstitial Lung Disease
  • lower dose glucocorticoid
  • cyclophosphamide
  • May require ventilatory support (NIPPV or Intubation)
• CREST Syndrome
  • Empiric treatment with a PPI to prevent reflux and stricture formation
  • Blood replacement if chronic loss from mucosal telangiectasias
  • Ursodial 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.
• Consult Rheumatology
• Consult Pulmonary
• Consult Nephrology