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1
Question:

A 44-year-old woman comes to the clinic after several near collisions over the past month while driving at night.  She also has generalized pruritus.  The patient has not seen a physician for several years and has missed several scheduled appointments.  She takes no medications.  On physical examination, she has patchy areas of coarse, thickened skin on the extremities.  Which of the following processes is most likely responsible for this patient's findings?

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Explanation:

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Vitamin A

Deficiency

Toxicity

Causes

  • Insufficient dietary intake (resource-limited regions)
  • Fat malabsorption (eg, pancreatic insufficiency, cholestasis, short bowel syndrome)
  • Dietary excess (eg, eggs, liver, kidney)
  • Medications (eg, retinoids)

Clinical features

  • Night blindness
  • Dry eyes, Bitot spots
  • Hyperkeratosis
  • Diminished immune response
  • Benign intracranial hypertension
  • Bone pain, fractures
  • Hepatomegaly
  • Dry skin & mucosa; alopecia
  • Teratogenic

This patient's impaired driving at night and coarse, thickened skin are suggestive of vitamin A deficiency.  Vitamin A is a lipid-soluble vitamin necessary for vision (phototransduction, retinal and conjunctival development) and keratinocyte differentiation.  Deficiency is characterized by night blindness and xerophthalmia (conjunctival and corneal dryness).  In some patients, abnormal conjunctival keratinization may lead to Bitot spots, or foamy white plaques in the eye.  Nonspecific dermatologic findings are also common and may include hyperkeratosis (thickened skin), as seen here.

Dietary intake of vitamin A comes from a combination of beta-carotene, a provitamin found in plants (eg, green leafy vegetables, carrots), and preformed vitamin A from animal sources (eg, eggs, liver, kidney).  In resource-rich regions, most individuals have adequate dietary intake of vitamin A, but patients may develop deficiency due to fat malabsorption related to biliary obstruction, exocrine pancreatic insufficiency (eg, cystic fibrosis), or small-bowel resection (eg, Crohn disease, bariatric surgery).

This patient with generalized pruritus and signs of vitamin A deficiency should be evaluated for primary biliary cholangitis (PBC), an autoimmune disease most common in middle-aged women and characterized by destruction of small intrahepatic bile ducts.  Because bile acids are important for solubilization and absorption of fats, patients with chronic biliary obstruction due to PBC may develop deficiency of fat-soluble vitamins (A, D, E, and K).  Generalized pruritus is common due to bile acid accumulation in the skin; jaundice is often not apparent until later in the disease course.

(Choices A and B)  Inadequate exposure to sunlight can cause vitamin D deficiency in individuals without adequate dietary vitamin D intake.  Chronic kidney disease can also result in vitamin D deficiency due to reduced production of 1,25-dihydroxyvitamin D.  Vitamin D deficiency is characterized by bone pain and fractures (eg, osteomalacia), not night blindness.

(Choice D)  Sickle cell disease is a form of chronic hemolytic anemia that can cause retinopathy due to microvascular vasoocclusion, retinal ischemia, and neovascularization/hemorrhage.  However, vision impairment would not be restricted to nighttime, and affected patients would likely have other vasoocclusive symptoms (eg, pain crises).

(Choice E)  A strict vegan diet is a risk factor for vitamin B12 (cobalamin), not vitamin A, deficiency.  Vitamin B12 deficiency presents with megaloblastic anemia (eg, fatigue, pallor) and neurologic deficits (eg, tingling, numbness).

Educational objective:
Vitamin A deficiency causes night blindness and hyperkeratosis.  Deficiency of this lipid-soluble vitamin can develop in patients with fat malabsorption due to chronic biliary obstruction, exocrine pancreatic insufficiency, or small-bowel resection.