At first glance, the diagnosis did not fit the patient’s profile. Further examination produced unexpected results.

Ms. W, a 53-year-old African American, had a two-day history of shortness of breath both at rest and during regular daily activities. She noted increased fatigue, constipation, and a 10- to 15-lb weight loss in the past six weeks secondary to nausea, vomiting, and decreased food intake. Her medical history was significant for gastroesophageal reflux disease and an unknown type of anemia warranting transfusion about two years earlier. She reported receiving IM vitamin B12 32 years ago. Her personal history was negative for tobacco or illicit drug use. She drank alcohol occasionally. Her only medication was folic acid, but the reason for this was unknown.


Ms. W’s vital signs were BP 128/66 mm Hg, heart rate regular at 81 beats per minute, respiration rate 20 breaths per minute, and temperature 99.9ºF. The patient had pearly white-to-gray hair, and she appeared pale. On oral examination, her tongue mucosa was moist, thick, and flattened. Guaiac stool test was negative. She complained of mild epigastric pain on palpation, but there was no guarding or rigidity. Neurologic examination revealed loss of proprioception as well as a positive Romberg’s sign with a wide waddling gait. Mild ankle edema was appreciated in both of the patient’s legs.

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Laboratory studies revealed severe pancytopenia and low vitamin B12. Hemoglobin was 4.9 g/dL, and hematocrit was 14.4%. Serum iron and ferritin were elevated at 175 µg/dL and 348 ng/mL, respectively. Moderate anisocytosis, poikilocytosis, and macrocytosis with slightly fragmented and teardrop cells were seen on the peripheral smear. Testing for intrinsic factor antibody (IFAb) was positive. Barium swallow studies showed faint gastric antral nodularity, and follow-up endoscopy revealed atrophic gastritis involving the gastric body and antrum. Helicobacter pylori testing was negative.


The patient’s history suggested anemia, but her symptoms suggested other differentials as well. MI was ruled out by negative results on three sets of cardiac enzymes and an absence of ECG changes. Esophagogastroduodenoscopy (EGD) and a negative gastric biopsy ruled out gastric ulcer and cancer.

Ms. W’s neurologic findings and history suggested a vitamin B12 deficiency. The clinical findings, supported by pancytopenia, low vitamin B12 levels, deficiency of intrinsic factor (based on a positive IFAb), as well as atrophic gastritis on EGD, confirmed the diagnosis of pernicious anemia. While absent in this case, a family history of pearly gray hair could be a clue as well.

Pernicious anemia is not commonly seen in the African-American population, but this diagnosis should always be considered in patients with shortness of breath, fatigue, and chest pain and then confirmed with appropriate testing.


Patients with pernicious anemia usually present with general symptoms of anemia, e.g., fatigue, weakness, and dyspnea. A five-P mnemonic can be used to describe the important clinical features for pernicious anemia:

Papillary atrophy of the tongue (atrophic glossitis)
Peripheral neuropathy (glove-and-stocking distribution of neuropathy)
Posterior spinal column neuropathy (decreased proprioception and vibration sense, ataxia and hyporeflexia with decreased ankle jerk), and
Pyramidal-tract signs (positive Babinski’s sign).

Depression, memory loss or forgetfulness, anorexia, palpitations, angina, and symptoms of heart failure have also been reported. Megaloblastic macrocytic anemia with pancytopenia (often with hypersegmented neutrophils), elevated serum methylmalonic acid, and homocysteine levels secondary to vitamin B12 deficiency are common laboratory findings.


Pernicious anemia, an autoimmune disorder, is usually characterized by atrophy of gastric mucosa and inability to absorb vitamin B12.1 Men and women are equally affected. Many patients are elderly. The higher prevalence of pernicious anemia among people of Northern European descent, followed by African Americans, was based primarily on the presence of anti-parietal cell antibody in older Caucasian patients.2 However, anti-parietal cell antibody has also been reported in cases of atrophic gastritis without pernicious anemia, while IFAb usually appears after patients develop pernicious anemia.2 IFAb binds the intrinsic factor needed for absorption of vitamin B12, leading to pernicious anemia.

While testing for pernicious anemia has traditionally been based on the Schilling test, IFAb, with an overall prevalence of 70% in patients with this anemia, has been reported to be a cost-effective and reliable diagnostic tool in the proper clinical settings.1 About 84% of African-American patients in this study had a positive IFAb compared with 55% of Caucasian and 69% of Latin American patients diagnosed with pernicious anemia.2 Only 13% of all participants were positive for anti-parietal cell antibody without the presence of IFAb; and about 30% had IFAb without anti-parietal cell antibody.

This low incidence of anti-parietal cell antibody with no IFAb or no anti-parietal antibody at all was more prevalent (44%) among African Americans than Caucasians (19%). These findings suggest a change in the previously published pattern of higher pernicious anemia in Caucasian elderly patients of European origin based on a positive finding of anti-parietal cell antibody.1

African-American patients have been reported to have a higher prevalence of IFAb compared with their Caucasian counterparts.2 Carmel reported higher numbers of younger patients with pernicious anemia among the African-American group compared with older participants and Caucasians of European origin. These observations may explain why a diagnosis of pernicious anemia in our patient would be considered atypical within a historic view of practice.

Earlier onset of pernicious anemia at a mean age of 53 years (SD +/-16 years) among African-American women compared with African-American males, Caucasians, and Latin Americans (P <.001) has also been reported.3,4 These findings make pernicious anemia an important consideration in middle-aged African-American women with symptoms of anemia.


Traditional therapy calls for vitamin B12 1 mg IM daily for seven days, followed by weekly dosing for one to two weeks, and then monthly for life.5 A less common oral regimen (1,000-2,000 µg/day for two weeks, then 1,000 µg/day for life) has also been effective.5 The usual recommendation for vitamin B12 in an adult is 2 µg/day.

Our patient received several blood transfusions for symptomatic relief. She then was started on long-term B12 supplementation IM, with the initial doses received during her inpatient admission. She showed significant clinical improvement while in the hospital and was discharged home on long-term outpatient vitamin B12 supplementation.

Dr. Rianon is a resident in the Department of Family and Community Medicine, University of Texas Houston Health Science Center, where Dr. Vasudevan is assistant professor in the same department.


1. Andres E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171:251-259.

2. Carmel R. Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race. Clin Exp Immunol. 1992;89:74-77.

3. Solanki DL, Jacobson RJ, Green R, et al. Pernicious anemia in blacks. A study of 64 patients from Washington, D.C., and Johannesburg, South Africa. Am J Clin Pathol. 1981;75:96-99.

4. Carmel R, Johnson CS. Racial patterns in pernicious anemia. Early age at onset and increased frequency of intrinsic-factor antibody in black women. N Engl J Med. 1978;298:647-650.

5. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67:979-986.