Faculty Development Case of the Month: November 2022

Monthly Case from the Department of Medicine

Young Healthy Male with Paresthesia, Ataxia, and Pancytopenia

Submitted by:
Mary Pelling, MS4
Department of Medicine

Edited by:
Yoo Mee Shin, MD
Assistant Professor
Hospital Medicine

Erica Han, MD
Assistant Professor
Hospital Medicine

Story and Case:

A 39-year-old man with no significant past medical history presented with four days of a constant “pins and needles” sensation located from his fingertips through elbows bilaterally, as well as progressive shortness of breath and fatigue. He also reported feeling unbalanced and light-headed. Additionally, for the past seven months, he had been experiencing worsening confusion, including word finding difficulties. Review of systems was positive for weight loss, night sweats, vision changes, and darkening of patient’s urine. Further history revealed a strict vegan diet for 20 years. He denied any tobacco or drug use and drank alcohol occasionally.

Vital signs were notable for a blood pressure of 85/48 mmHg, heart rate of 60 bpm, and normal oxygen saturation. Physical exam showed sublingual pallor and slow conversational speech but was otherwise normal. Laboratory results revealed pancytopenia with white blood cell count of 1,700 microliter (mcL), hemoglobin of 4.5 gm/dL, mean corpuscular volume of 103 fl, and platelets of 111,000 microliter. Other labs included an Indirect bilirubin which was elevated at 1.74 mg/dL with a low reticulocyte index of 0.1, an elevated lactate dehydrogenase greater than 3600 unit/L, and a low haptoglobin of less than 3 mg/dL, but a negative direct anticoagulant test. Blood smear revealed hypersegmented neutrophils as well as marked macrocytosis. Vitamin B12 level was undetectable at less than 50 pg/mL, but folic acid was normal at 16.2 ng/mL. Anti-intrinsic factor and parietal cell antibodies were negative. Thorough workup included syphilis, HIV, viral hepatitis panel, Cytomegalovirus, Epstein-Barr virus, Parvovirus, and Systemic lupus erythematosus (SLE), all of which were unremarkable.  Thyroid stimulating hormone was slightly increased to 8.27 uIU/mL with mildly low triiodothyronine 71 ng/dL and normal free thyroxine. Computerized tomography (CT) head without contrast was unrevealing with no acute abnormalities noted. Abdominal and pelvis CT with IV contrast was also unrevealing, with only a small hypodensity in the right hepatic lobe, making malignancy less likely.

What’s the Diagnosis?

A comprehensive differential was formed including malignant (leukemia, lymphoma, myelodysplastic syndrome), infectious (HIV, hepatitis, viral etiologies, syphilis), autoimmune (SLE, pernicious anemia, autoimmune gastritis), hematologic (hemophagocytic lymphohistiocytosis), nutritional (B12 and folate deficiency), and endocrine (hypothyroidism) etiologies. As the patient was also found to have severe B12 deficiency, this diagnosis seemed to offer a cohesive explanation for this patient’s symptoms. Therapeutic interventions for B12 deficiency led to a rapid improvement which ultimately led to the diagnosis.

During the patient’s hospital stay, he received three units of packed red blood cells and two subcutaneous doses of 1000 mcg B12 with rapid improvement in mental status, ataxia, and paresthesia. The patient was discharged with five more doses of Vitamin B12 1000 mcg/mL injectable solution to use daily for a total of seven consecutive daily doses. He was instructed to administer a dose once weekly for four weeks and then once monthly. He was discharged with hematology and primary care follow-up appointments.

At the one-month follow-up, the patient’s confusion had resolved, and only mild residual left-hand paresthesia remained. After two months, all his hematologic and other relevant labs improved and his B12 level normalized. White blood cell count improved to 3.0 k/mcL, hemoglobin was 13.8 gm/dL with an MCV of 88.5 fL, and platelets were 243 k/mcL. Vitamin B12 level was 327 pg/mL.

FINAL DIAGNOSIS?

Vitamin B12 deficiency secondary to 20 years of a strict vegan diet.

DISCUSSION

Anemia related to B12 (cobalamin) deficiency is most frequently due to pernicious anemia or prior gastrointestinal surgery and much less commonly results from dietary deficiency. However, with increasing rates of veganism and vegetarian diets, B12 deficiency prevalence has been increasing. Vitamin B12, found primarily in animal products, is an important cofactor in DNA and RNA synthesis. A deficiency leading to clinical consequences typically takes 1–4 years to develop, with hematologic and neurologic symptoms being the most evident.

After treatment with supplemental B12, anemia usually completely resolves in 4–6 weeks. Recovery from neurologic symptoms can take several months after supplementation and in some cases symptoms are permanent. Therefore, it is imperative to start treatment to replenish B12 when clinical suspicion is high. Neurologic symptoms, such as word-finding difficulty in this patient, are an exception and can improve rapidly.

CITATIONS

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