A 64-year-old Caucasian woman complains of gradually increasing tiredness. She feels the cold more than she used to. She also has a sore tongue. Over the past 2 months, she has complained of numbness of her feet. She eats a normal diet. Her sister has hypothyroidism.
On examination, she is pale and slightly jaundiced. Her tongue is reddened and enlarged; she has grey hair. The thyroid gland is clinically normal. She has reduced touch and joint position sense in the toes and the ankle jerks are absent. Neurological examination is otherwise normal.
Investigations show:
Hb 64 g/L
MCV 131 fl
WBC 3.1 × 109/L
Platelets 63 × 109/L.
Blood film – as illustrated.
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(a) What is the differential diagnosis?
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Correct answer: Megaloblastic anaemia due to vitamin B12 or folate deficiency is the most common cause. Pernicious anaemia is an autoimmune gastritis which occurs in association with autoimmune hypothyroidism; it causes vitamin B12 deficiency.
Folate deficiency due to poor diet (which she denies) or malabsorption is possible.
Other causes of a macrocytic anaemia include liver disease, the presence of a paraprotein and myelodysplasia. However, the presence of an MCV greater than 120 fl is rarely seen outside megaloblastic anaemia.
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(b) Which further investigations are required?
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Correct answer:
(1) Serum levels of vitamin B12 and folate should be checked.
(2) Serum ferritin as iron deficiency often coexists.
(3) Thyroid function, liver function, protein electrophoresis.
(4) Antibodies to gastric parietal cells, intrinsic factor and thyroid autoantibodies should be assessed.
(5) Bone marrow examination is now rarely performed.
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(c) How would you treat her?
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Correct answer: She should have the blood tests done first and then receive 1000 µg hydroxocobalamin by injection. It is important to give the B12 first, as administration of B12 to an indicidual with folate deficiency can precipitate neurological complications of B12 deficiency. Other haematinic deficiencies, including folate and iron, should also be corrected. Thyroid deficiency should be treated. Blood transfusion should be avoided as there is a risk of fluid overload if anaemia is rapidly corrected in an elderly individual with long-standing anaemia. Six injections of hydroxocobalamin should be given over 2-3 weeks and then every 3 months for life.
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(d) What complications can occur?
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Correct answer: There is an increased risk of gastric cancer in patients with pernicious anaemia. Subacute combined degeneration of the spinal cord is a neurological complication presenting as peripheral neuropathy (e.g. numbness, tingling in the legs with loss of ankle reflexes) with weakness and unsteadiness (often with upper motor neurone signs in the legs, including increased knee reflexes, upgoing plantars) of the limbs. Vitiligo is an autoimmune skin condition which presents with patchy areas of hypopigmentation. Addison disease is autoimmune hypoadrenalism and may also occur. Melanin skin pigmentation may occur and resolves with B12 therapy.
