HPI
•58 year old African American female
presents to your clinic with one month
history of fatigue and shortness of
breath.
•What else would you like to know?
HPI continued
• Patient states that the shortness of breath usually
occurs when she is climbing stairs or walking down
the long hallway in her house.
• She says for the past month she has not had much of
an appetite, and she has been experiencing
diarrhea.
• She reports numbness and tingling in her fingers and
toes.
Medical History
• Past medical history: Hashimoto’s thyroiditis
• Past surgical history: Hysterectomy at age 45
• Medications: Synthroid (synthetic thyroid hormone)
• Social History: Single. Retired administrative assistant.
Denies smoking, alcohol, illicit drugs.
• What is on our differential diagnosis?
Differential Diagnosis
• Hypothyroidism
• Malignancy
• Malabsorption syndrome (ie Zollinger-Ellison syndrome)
• Infection (ie D. latum tapeworm)
• Anemia
– Aplastic anemia
– Hemolytic anemia
– Pernicious anemia
• Depression
What would you like to do
next??
Physical Exam
• Vitals: Temp 98.6F, Pulse 110, Resp 20, BP 130/85
• General: Well-nourished African American female. No acute distress.
• HEENT: Pale conjunctiva, angular cheilitis, glossitis.
• Cardio: Mildly tachycardic. Regular rhythym. No murmurs, rubs, or gallops.
• Resp: Breath sounds clear bilaterally to auscultation. Non-labored
breathing while sitting.
• Neuro:
-Diminished sensation to vibration bilaterally in upper and
lower extremities. Intact proprioception. Mild ataxia during
heel-toe walking. Romberg test positive.
What tests should we order?
Laboratory Tests
•
WBC 45000 (normal) , Hgb 9.0 (low) , Hematocrit 27.0 (low) ,
•
MCV 115 (increased)
•
B12 level: 100 pg/ml (low)
•
Folate level: 10 ng/ml (normal)
•
Methylmalonic acid: 0.6 umol/L (elevated)
•
Homocysteine: 15 mcmol/L (elevated)
•
Serum intrinsic factor blocking antibody: present
•
Gastrin: 300 pg/ml (elevated)
Peripheral smear
• Findings:
-Hypersegmented neutrophil (seven lobes)
-Macroovalocytes
• In light of the lab results and peripheral smear, what is
your diagnosis?
Resolution
• Patient was diagnosed with
pernicious anemia.
•Patient was begun on lifelong B12
replacement therapy.
Pernicious Anemia
• Pernicious anemia is a classification of B12 deficiency
which is caused by a lack of intrinsic factor from the
stomach’s parietal cells.
• B12 gets absorbed in the terminal ileum only when
bound to intrinsic factor. Without the intrinsic factor,
the body will not be able to absorb B12.
• Two common causes of pernicious anemia:
– Antibody to IF (in the case of our patient)
– Atrophic gastritis (IF is not being produced properly)
Clinical Presentation
Patients with pernicious anemia can present with a variety of issues
including:
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•
•
•
•
•
•
•
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Weakness
Fatigue
Shortness of breath
Ataxia
Loss of proprioception
Peripheral neuropathy
Poor coordination
Personality changes
Glossitis (tongue inflammation)
Angular chelitis (inflammation/cracking in the corners of the
mouth)
• Changes in bowel habits (constipation or diarrhea)
Evaluating MMA and Homocysteine
Patient Condition
Healthy
Vitamin B-12 deficiency
Folate deficiency
MethylmalonicAcid
Normal
Elevated
Normal
Homocysteine
Normal
Elevated
Elevated
This diagram reminds us
about the metabolism of
MMA and homocysteine.
Diagnosis
• Once it is found that the patient has a macrocytic anemia (low
hemoglobin with elevated MCV), evaluation of the MMA and
homocysteine levels can then help confirm the etiology.
• The Schilling Test can also be employed, in which B12 and
intrinsic factor are given in different monitored stages to
determine the etiology of the B12 deficiency.
• Usually a bone marrow biopsy is not needed for diagnosis. Below
is a picture of a normal bone marrow biopsy on the left, and a
biopsy of a patient with pernicious anemia on the right.
Megaloblastic
erythropoeisis is
seen in both B12
and folate
deficiency bone
marrow samples.
Treatment
• Lifelong B12 replacement therapy is ordinarily required for
a patient with pernicious anemia.
• The regimen begins with 1000 mcg injection daily for a
week, then 1 mg weekly for a month, then usually 1 mg
every month for the remainder of the patient’s life.
• It takes time for the neurological symptoms to improve
(numbness and tingling, with our patient). Between 6
months and a year after beginning treatment, usually a
patient’s neurological symptoms are the most improved
they will ever be. If the anemia has been going on for an
extended time before treatment, some symptoms may
never fully improve.