Jonathan Zhang, MD

In Reply: We thank Dr. Phillips for his inquiry.

In general, serum vitamin B₁₂ concentrations vary greatly, and we acknowledge that serum vitamin B₁₂ may be normal in up to 5% of patients with documented B₁₂ deficiency.¹ In a prospective study of 1,599 patients, Matchar et al² demonstrated that a single vitamin B₁₂ level less than 200 pg/mL had a specificity greater than 95% at predicting vitamin B₁₂ deficiency.² We acknowledge that additional metabolite testing is necessary in equivocal cases in which the vitamin B₁₂ level is between 200 and 300 pg/mL, which is often considered to be the normal range, but the patient has symptoms of vitamin B₁₂ deficiency such as dementia and unexplained macrocytosis, and neurologic symptoms.³

Based on the patient’s symptoms of neuropathy and fatigue in conjunction with a vitamin B₁₂ level well below 200 pg/mL, we believe that the diagnosis can be made.^2,3 Nonetheless, although we did not mention it in our article, we did indeed send for a methylmalonic acid measurement at the time of the initial evaluation, and the level was elevated at 396 nmol/L (normal 87–318 nmol/L), further confirming her vitamin B₁₂ deficiency.

In Reply: We thank Dr. Phillips for his inquiry.

In general, serum vitamin B₁₂ concentrations vary greatly, and we acknowledge that serum vitamin B₁₂ may be normal in up to 5% of patients with documented B₁₂ deficiency.¹ In a prospective study of 1,599 patients, Matchar et al² demonstrated that a single vitamin B₁₂ level less than 200 pg/mL had a specificity greater than 95% at predicting vitamin B₁₂ deficiency.² We acknowledge that additional metabolite testing is necessary in equivocal cases in which the vitamin B₁₂ level is between 200 and 300 pg/mL, which is often considered to be the normal range, but the patient has symptoms of vitamin B₁₂ deficiency such as dementia and unexplained macrocytosis, and neurologic symptoms.³

Based on the patient’s symptoms of neuropathy and fatigue in conjunction with a vitamin B₁₂ level well below 200 pg/mL, we believe that the diagnosis can be made.^2,3 Nonetheless, although we did not mention it in our article, we did indeed send for a methylmalonic acid measurement at the time of the initial evaluation, and the level was elevated at 396 nmol/L (normal 87–318 nmol/L), further confirming her vitamin B₁₂ deficiency.

In Reply: We thank Dr. Phillips for his inquiry.

In general, serum vitamin B₁₂ concentrations vary greatly, and we acknowledge that serum vitamin B₁₂ may be normal in up to 5% of patients with documented B₁₂ deficiency.¹ In a prospective study of 1,599 patients, Matchar et al² demonstrated that a single vitamin B₁₂ level less than 200 pg/mL had a specificity greater than 95% at predicting vitamin B₁₂ deficiency.² We acknowledge that additional metabolite testing is necessary in equivocal cases in which the vitamin B₁₂ level is between 200 and 300 pg/mL, which is often considered to be the normal range, but the patient has symptoms of vitamin B₁₂ deficiency such as dementia and unexplained macrocytosis, and neurologic symptoms.³

Based on the patient’s symptoms of neuropathy and fatigue in conjunction with a vitamin B₁₂ level well below 200 pg/mL, we believe that the diagnosis can be made.^2,3 Nonetheless, although we did not mention it in our article, we did indeed send for a methylmalonic acid measurement at the time of the initial evaluation, and the level was elevated at 396 nmol/L (normal 87–318 nmol/L), further confirming her vitamin B₁₂ deficiency.

A 76-year-old woman visiting from Ethiopia presented for further evaluation of concomitant iron and vitamin B₁₂ deficiency anemia that had developed over the previous 6 months. During that time, she had complained of ongoing fatigue and increasing paresthesias in the hands and feet.

At presentation, her hemoglobin concentration was 7.8 g/dL (reference range 11.5–15), with a mean corpuscular volume of 81.8 fL (81.5–97.0). These values were down from her baseline hemoglobin of 12 g/dL and corpuscular volume of 85.8 recorded more than 1 year ago. Serum studies showed an iron concentration of 21 µg/dL (37–170), ferritin 3 ng/mL (10–107), and percent saturation of transferrin 5% (20%–55%). Also noted was a low vitamin B₁₂ level of 108 pg/mL (180–1,241 pg/mL). She had no overt signs of gastrointestinal blood loss. She did not report altered bowel habits or use of nonsteroidal anti-inflammatory medications.

Given her country of origin, she was sent for initial stool testing for ova and parasites, which was unrevealing.

She underwent esophagogastroduodenoscopy and colonoscopy, which revealed no underlying cause of her iron deficiency or vitamin B₁₂ insufficiency. But further evaluation with capsule endoscopy showed evidence of a tapeworm in the distal duodenum (Figure 1).

She was given praziquantel in a single oral dose of 10 mg/kg. Repeat stool culture 1 month later showed no evidence of tapeworm infection, and at follow-up 3 months later, her hemoglobin had recovered to 13.2 g/dL with a corpuscular volume of 87.6 fL and no residual vitamin B₁₂ or iron deficiency. She reported complete resolution of fatigue and of paresthesias of the hands and feet.

DIPHYLLOBOTHRIUM LATUM

The appearance on capsule endoscopy indicated Diphyllobothrium latum as the likely parasite. This tapeworm is acquired by ingesting undercooked or raw fish. Infection is most common in Northern Europe but has been reported in Africa.¹

As it grows, the tapeworm develops chains of segments and can reach a length of 1 to 15 meters.¹ In humans, it typically resides in the small intestine. Most patients are asymptomatic or have moderate nonspecific symptoms such as abdominal pain and diarrhea. A key differentiating aspect of D latum infection is vitamin B₁₂ deficiency caused by consumption of the vitamin by the parasite, as well as by parasite-mediated dissociation of the vitamin B₁₂-intrinsic factor complex, thus making the vitamin unavailable to the host.

Up to 40% of people infected with D latum develop low levels of vitamin B₁₂, and 2% develop symptomatic megaloblastic anemia.² Iron deficiency anemia is uncommon but has been reported.³ In our patient, the concomitant iron deficiency was probably secondary to involvement of the duodenum, where a significant amount of dietary iron is absorbed.

The diagnosis is typically established by stool testing for ova and parasites. When stool samples do not reveal a cause of the symptoms, as in this patient, endoscopy can be used. Capsule endoscopy has not been widely used in the diagnosis of intestinal helminth infection, although reports exist describing the use of capsule endoscopy to detect intestinal parasites. Notably, as in this case, intestinal parasite infection is occasionally found during investigations of anemia and vitamin deficiencies of unknown cause.⁴

As in our patient, treatment of infection with this species of tapeworm typically involves a single oral dose of praziquantel; this off-label use has been shown to lead to resolution of symptoms in nearly all patients treated.⁵

A 76-year-old woman visiting from Ethiopia presented for further evaluation of concomitant iron and vitamin B₁₂ deficiency anemia that had developed over the previous 6 months. During that time, she had complained of ongoing fatigue and increasing paresthesias in the hands and feet.

At presentation, her hemoglobin concentration was 7.8 g/dL (reference range 11.5–15), with a mean corpuscular volume of 81.8 fL (81.5–97.0). These values were down from her baseline hemoglobin of 12 g/dL and corpuscular volume of 85.8 recorded more than 1 year ago. Serum studies showed an iron concentration of 21 µg/dL (37–170), ferritin 3 ng/mL (10–107), and percent saturation of transferrin 5% (20%–55%). Also noted was a low vitamin B₁₂ level of 108 pg/mL (180–1,241 pg/mL). She had no overt signs of gastrointestinal blood loss. She did not report altered bowel habits or use of nonsteroidal anti-inflammatory medications.

Given her country of origin, she was sent for initial stool testing for ova and parasites, which was unrevealing.

She underwent esophagogastroduodenoscopy and colonoscopy, which revealed no underlying cause of her iron deficiency or vitamin B₁₂ insufficiency. But further evaluation with capsule endoscopy showed evidence of a tapeworm in the distal duodenum (Figure 1).

She was given praziquantel in a single oral dose of 10 mg/kg. Repeat stool culture 1 month later showed no evidence of tapeworm infection, and at follow-up 3 months later, her hemoglobin had recovered to 13.2 g/dL with a corpuscular volume of 87.6 fL and no residual vitamin B₁₂ or iron deficiency. She reported complete resolution of fatigue and of paresthesias of the hands and feet.

DIPHYLLOBOTHRIUM LATUM

The appearance on capsule endoscopy indicated Diphyllobothrium latum as the likely parasite. This tapeworm is acquired by ingesting undercooked or raw fish. Infection is most common in Northern Europe but has been reported in Africa.¹

As it grows, the tapeworm develops chains of segments and can reach a length of 1 to 15 meters.¹ In humans, it typically resides in the small intestine. Most patients are asymptomatic or have moderate nonspecific symptoms such as abdominal pain and diarrhea. A key differentiating aspect of D latum infection is vitamin B₁₂ deficiency caused by consumption of the vitamin by the parasite, as well as by parasite-mediated dissociation of the vitamin B₁₂-intrinsic factor complex, thus making the vitamin unavailable to the host.

Up to 40% of people infected with D latum develop low levels of vitamin B₁₂, and 2% develop symptomatic megaloblastic anemia.² Iron deficiency anemia is uncommon but has been reported.³ In our patient, the concomitant iron deficiency was probably secondary to involvement of the duodenum, where a significant amount of dietary iron is absorbed.

The diagnosis is typically established by stool testing for ova and parasites. When stool samples do not reveal a cause of the symptoms, as in this patient, endoscopy can be used. Capsule endoscopy has not been widely used in the diagnosis of intestinal helminth infection, although reports exist describing the use of capsule endoscopy to detect intestinal parasites. Notably, as in this case, intestinal parasite infection is occasionally found during investigations of anemia and vitamin deficiencies of unknown cause.⁴

As in our patient, treatment of infection with this species of tapeworm typically involves a single oral dose of praziquantel; this off-label use has been shown to lead to resolution of symptoms in nearly all patients treated.⁵

A 76-year-old woman visiting from Ethiopia presented for further evaluation of concomitant iron and vitamin B₁₂ deficiency anemia that had developed over the previous 6 months. During that time, she had complained of ongoing fatigue and increasing paresthesias in the hands and feet.

At presentation, her hemoglobin concentration was 7.8 g/dL (reference range 11.5–15), with a mean corpuscular volume of 81.8 fL (81.5–97.0). These values were down from her baseline hemoglobin of 12 g/dL and corpuscular volume of 85.8 recorded more than 1 year ago. Serum studies showed an iron concentration of 21 µg/dL (37–170), ferritin 3 ng/mL (10–107), and percent saturation of transferrin 5% (20%–55%). Also noted was a low vitamin B₁₂ level of 108 pg/mL (180–1,241 pg/mL). She had no overt signs of gastrointestinal blood loss. She did not report altered bowel habits or use of nonsteroidal anti-inflammatory medications.

Given her country of origin, she was sent for initial stool testing for ova and parasites, which was unrevealing.

She underwent esophagogastroduodenoscopy and colonoscopy, which revealed no underlying cause of her iron deficiency or vitamin B₁₂ insufficiency. But further evaluation with capsule endoscopy showed evidence of a tapeworm in the distal duodenum (Figure 1).

She was given praziquantel in a single oral dose of 10 mg/kg. Repeat stool culture 1 month later showed no evidence of tapeworm infection, and at follow-up 3 months later, her hemoglobin had recovered to 13.2 g/dL with a corpuscular volume of 87.6 fL and no residual vitamin B₁₂ or iron deficiency. She reported complete resolution of fatigue and of paresthesias of the hands and feet.

DIPHYLLOBOTHRIUM LATUM

The appearance on capsule endoscopy indicated Diphyllobothrium latum as the likely parasite. This tapeworm is acquired by ingesting undercooked or raw fish. Infection is most common in Northern Europe but has been reported in Africa.¹

As it grows, the tapeworm develops chains of segments and can reach a length of 1 to 15 meters.¹ In humans, it typically resides in the small intestine. Most patients are asymptomatic or have moderate nonspecific symptoms such as abdominal pain and diarrhea. A key differentiating aspect of D latum infection is vitamin B₁₂ deficiency caused by consumption of the vitamin by the parasite, as well as by parasite-mediated dissociation of the vitamin B₁₂-intrinsic factor complex, thus making the vitamin unavailable to the host.

Up to 40% of people infected with D latum develop low levels of vitamin B₁₂, and 2% develop symptomatic megaloblastic anemia.² Iron deficiency anemia is uncommon but has been reported.³ In our patient, the concomitant iron deficiency was probably secondary to involvement of the duodenum, where a significant amount of dietary iron is absorbed.

The diagnosis is typically established by stool testing for ova and parasites. When stool samples do not reveal a cause of the symptoms, as in this patient, endoscopy can be used. Capsule endoscopy has not been widely used in the diagnosis of intestinal helminth infection, although reports exist describing the use of capsule endoscopy to detect intestinal parasites. Notably, as in this case, intestinal parasite infection is occasionally found during investigations of anemia and vitamin deficiencies of unknown cause.⁴

As in our patient, treatment of infection with this species of tapeworm typically involves a single oral dose of praziquantel; this off-label use has been shown to lead to resolution of symptoms in nearly all patients treated.⁵