Updated: 5/27/2019

Antitrypsin Deficiency

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Snapshot
  • A 24-year-old woman with a past medical history of atopic dermatitis presents to an urgent care center for dyspnea on exertion. She reports that for the past few months, she has become increasingly short of breath with exertion, particularly during exercise. She denies any other symptoms and denies having ever smoked or been exposed chronically to second-hand smoke. Close examination into her pediatric records shows a documented history of hepatomegaly but no workup. Labs reveal significantly decreased alpha-1 antitrypsin and increased transaminitis. She is given nebulized ipratropium and albuterol, a course of steroids, and referred for regular treatments with alpha-1 antitrypsin.
Introduction
  • Clinical definition
    • alpha-1 antitrypsin deficiency is characterized by
      • early-onset emphysema
      • cirrhosis
  • Epidemiology
    • demographics
      • young adults
        • often without a history of smoking
    • risk factors
      • family history
      • smoking exacerbates illness
  • Pathogenesis
    • alpha-1 antitrypsin is a serine protease inhibitor synthesized in the liver
      • inhibits proteolysis by enzymes, particularly elastase
    • decrease or dysfunctional alpha-1 antitrypsin is usually caused by misfolded gene product
      • increased proteolysis of alveoli by neutrophil elastase
      • accumulation of the misfolded alpha-1 antitrypsin polymers in hepatocytes
      • proteolysis and damage to vessels may cause vasculitis
  • Genetics
    • autosomal codominant
    • SERPINA1 gene
Presentation
  • Symptoms
    • chronic obstructive pulmonary disease (COPD)
      • onset at age 40-50 years
      • dyspnea on exertion
      • wheezes
      • cough
      • sputum production
    • liver disease that may progress to cirrhosis
      • onset in childhood
      • hepatomegaly
      • abdominal pain
Studies
  • Diagnostic testing
    • imaging
      • chest radiograph
        • findings
          • flattened diaphragm
      • computed tomography of chest
        • findings
          • panacinar emphysema
    • studies
      • ↑ prothrombin time
      • ↓ alpha-1 antitrypsin level
      • ↑ liver enzymes
      • genetic testing
        • confirms diagnosis
      • liver biopsy
        • often not needed
        • findings
          • PAS+ globules in hepatocytes
  • Diagnostic criteria
    • diagnosed with ↓ alpha-1 antitrypsin levels and confirmed with genetic testing or liver biopsy
Differential
  • Asthma
    • distinguishing factor
      • typically not associated with liver disease and presents at a younger age
  • Autoimmune hepatitis 
    • distinguishing factor
      • typically not associated with COPD or ↓ alpha-1 antitrypsin levels
Treatment
  • First-line
    • alpha-1 antitrypsin infusion
      • indication
        • patients with symptoms of COPD
    • standard COPD treatment
  • Second-line
    • liver transplant
      • indication
        • decompensated cirrhosis
        • hepatocellular carcinoma
      • outcomes
        • liver transplant will help patients maintain normal levels of donor’s alpha-1 antitrypsin
  • Other treatments
    • vaccinations
      • influenza
      • pneumococcus
    • minimize alcohol consumption
Complications
  • Hepatocellular carcinoma
    • regular surveillance
      • liver ultrasound
      • alpha-fetoprotein

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