A 59 Year Old Man.fatigue.abdominalpain

case records of the massachusetts general hospital

T h e n e w e ngl a nd j o u r na l o f m e dic i n e

n engl j med 370;16 nejm.org april 17, 20141542

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From the Departments of Medicine (L.S.F., L.H.S.) and Pathology (A.R.S.), Massachu-setts General Hospital, the Departments of Medicine (L.S.F., L.H.S., R.H.G.) and Pathology (A.R.S.), Harvard Medical School, and the Department of Medicine, Tufts University School of Medicine (L.S.F.), Bos-ton; the Department of Medicine, Newton-Wellesley Hospital, Newton (L.S.F.); and the Department of Medicine, Cambridge Health Alliance, Cambridge (R.H.G.) — all in Massachusetts.

N Engl J Med 2014;370:1542-50.DOI: 10.1056/NEJMcpc1314242Copyright © 2014 Massachusetts Medical Society.

Pr esen tation of C a se

Dr. Laura D. Flannery (Medicine): A 59-year-old man was seen in an outpatient clinic at this hospital because of fatigue, abdominal pain, anemia, arthralgias, and abnormal liver function.

The patient had been in his usual state of health until approximately 3 days before presentation, when epigastric distress and ankle edema occurred. He also reported increased personal stress, difficulty sleeping, dysgeusia, and nausea. On presentation in an outpatient clinic at this hospital, he reported epigastric pain that he rated at 6 on a scale of 0 to 10 (with 10 indicating the most severe pain) and no weight loss. He had a history of asthma, pain and effusion of the right knee associated with a Baker’s cyst, occasional swelling of the right ankle, and varicose veins. He had had normal results on colonoscopy 3 years earlier. His medications were pirbuterol by inhalation as needed for asthma and sucralfate as needed for stomach discomfort; he reported no use of nonsteroidal antiinflamma-tory drugs. He lived with his partner and worked in an office. He consumed two or three glasses of wine per night and did not smoke or use illicit drugs.

On examination, the temperature was 37.3°C, the blood pressure 110/68 mm Hg, the weight 81.8 kg, and the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) 25.8. There was pitting edema of the ankles and superficial varicosities of both legs; the remainder of the examina-tion was normal. The mean corpuscular hemoglobin and the mean corpuscular hemoglobin concentration were normal, as were results of renal-function tests and blood levels of calcium, total protein, albumin, amylase, and alkaline phosphatase. Other test results are shown in Table 1 and revealed a new anemia as compared with test results from 4 months earlier, which included a hematocrit of 42% and a mean corpuscular volume of 88 μm3. Review of a peripheral-blood smear revealed 1+ polychromasia and basophilic stippling (Fig. 1). A diagnosis of gastroenteritis was made, with possible peptic-ulcer disease and a bleeding ulcer. Omeprazole and sucralfate were administered, tests for blood in the stool and for antibodies to

Case 12-2014: A 59-Year-Old Man with Fatigue, Abdominal Pain, Anemia,

and Abnormal Liver FunctionLawrence S. Friedman, M.D., Leigh H. Simmons, M.D.,

Rose H. Goldman, M.D., M.P.H., and Aliyah R. Sohani, M.D.

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case records of the massachusetts gener al hospital

n engl j med 370;16 nejm.org april 17, 2014 1543

Table 1. Laboratory Data.*

VariableReference Range,

Adults†On Presentation, Outpatient Clinic

2 Days after Presentation,

Emergency Department

3 Days after Presentation, Outpatient Clinic

5 Days after Presentation,

On Admission, Emergency Department

Hematocrit (%) 41.0–53.0 30.6 30.1 30.6 31.6

Hemoglobin (g/dl) 13.5–17.5 9.9 10.3 10.5 11.2

White-cell count (per mm3) 4500–11,000 7500 8900 10,000 11,100

Differential count (%)

Neutrophils 40–70 63.0 83.0 80.0 69.6

Band forms 0–10 1.0 1.0 2.0

Lymphocytes 22–44 20.0 12.0 9.0 14.4

Monocytes 4–11 10.0 4.0 8.0 14.5

Eosinophils 0–8 3.0 0 0 0.7

Basophils 0–3 3.0 0 0 0.3

Metamyelocytes 0 0 0 1.0

Nucleated red cells (per 100 white cells)

0 7 3 3 1

Platelet count (per mm3) 150,000–400,000 338,000 306,000, large forms present

351,000, large forms present

365,000

Mean corpuscular volume (μm3) 80–100 83 79 81 79

Erythrocyte count (per mm3) 4,500,000–5,900,000 3,680,000 3,790,000 3,790,000 4,010,000

Red-cell distribution width (%) 11.5–14.5 15.3 14.6 14.9 14.7

Smear description 1+ polychromasia, basophilic stippling

1+ polychromasia, basophilic stippling

2+ polychromasia, basophilic stippling

Not performed

Erythrocyte sedimentation rate (mm/hr) 0–13 3

Sodium (mmol/liter) 135–145 138 136 133 126

Potassium (mmol/liter) 3.4–4.8 4.1 3.6 3.9 3.4

Chloride (mmol/liter) 100–108 101 99 96 88

Carbon dioxide (mmol/liter) 23.0–31.9 23.8 25.8 25.4

Glucose (mg/dl) 70–110 70 118 151 114

Bilirubin (mg/dl)

Total 0.0–1.0 0.7 1.4 1.4 1.8

Direct 0.0–0.4 0.1 0.3 0.4

Globulin (g/dl) 2.3–4.1 1.6 1.6 1.9 1.7

Phosphorus (mg/dl) 2.6–4.5 2.6 1.9

Magnesium (mg/dl) 1.7–2.4 1.7 1.6

Alkaline phosphatase (U/liter) 45–115 82 83 81 89

Aspartate aminotransferase (U/liter) 10–40 89 84 84 179

Alanine aminotransferase (U/liter) 10–55 219 201 203 349

Lipase (U/liter) 13–60 76 30 28

C-reactive protein (mg/liter) <8.0 for inflammation 0.9

Iron (μg/dl) 45–160 166

Iron-binding capacity (μg/dl) 230–404 211

Ferritin (ng/ml) 30–300 274

* To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for bilirubin to micromoles per liter, multiply by 17.1. To convert the values for phosphorus to millimoles per liter, multiply by 0.3229. To convert the values for magnesium to millimoles per liter, multiply by 0.4114. To convert the values for iron and iron-binding capacity micromoles per liter, multiply by 0.1791.

† Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They may therefore not be appropriate for all patients.





Helicobacter pylori in the blood were ordered, an upper endoscopy was scheduled, and a bland diet was recommended. The patient was in-structed to follow up in 3 days, or sooner if his condition worsened.

The next day, the patient called his doctor’s office to report pain in both legs and increasing dysgeusia. He reported that his stools were looser than usual, without hematochezia or melena. The following day, 2 days after presentation, he was seen by his primary care physician in an outpa-tient clinic at this hospital. He reported increased abdominal pain, pain in the right knee and both shoulders, and fatigue that had lasted for at least 1 week. On examination, the temperature was

37.2°C, the blood pressure 131/89 mm Hg, the pulse 89 beats per minute, the height 177.8 cm, the weight 80.3 kg, and the BMI 25.4. The abdo-men was normal, and the right knee was tender on palpation, with a mild effusion and no erythema; the remainder of the examination was normal. Stool obtained during a rectal examination was negative for occult blood. The patient scheduled a follow-up visit and returned home.

That night, the patient presented to the emer-gency department at this hospital because of diffuse abdominal pain that was worse with eating and radiated to the left side of the chest, neck, shoulder, and back. Pain that was initially intermittent had become constant, and he had had constipation for 2 days. On examination, the blood pressure was 187/90 mm Hg; other vital signs, the oxygen saturation, and the remainder of the examination were normal. The blood level of lactic acid and results of coagulation tests were normal, and testing for antibodies to H. pylori in the blood and for blood in the stool was nega-tive; other test results are shown in Table 1. Urinalysis revealed trace ketones and was other-wise normal. Abdominal ultrasonography was normal. Oxycodone and ondansetron were ad-ministered. The patient was advised to avoid acetaminophen and alcohol, and he went home in the early morning hours.

Later that morning, the patient returned to the hospital for an outpatient visit and rated the pain at 4 out of 10. He had hypoactive bowel sounds and periumbilical fullness, with no epigastric pain on palpation. The blood level of C-reactive protein was normal, and testing for antibodies to hepati-tis C virus, antibodies to the human immunode-ficiency virus (HIV), and HIV antigen was nega-tive; other test results are shown in Table 1. The next day, upper endoscopic examination revealed a hiatal hernia, a nonobstructing Schatzki’s ring at the gastroesophageal junction, and nodularity in the duodenal bulb. That evening, the abdomi-nal pain markedly increased.

The next day, 5 days after the patient’s initial presentation, he returned to the outpatient clin-ic. He reported pain in the lower abdomen (rated at 8 out of 10), constipation that had lasted for 4 days, nausea with dry heaves, shortness of breath, and insomnia due to pain. On examina-tion, he was tearful and writhing in discomfort. The temperature was 37.5°C, the blood pressure

A

B

Figure 1. Peripheral-Blood Smear (Wright–Giemsa stain).

Review of a peripheral-blood smear reveals several erythrocytes with coarse basophilic stippling (Panel A, arrows), as evidenced by punctate basophilic inclu-sions that are evenly distributed throughout the cyto-plasm. Some red cells are enlarged, with a purplish hue (arrowheads); this polychromasia reflects increased numbers of circulating reticulocytes. A few nucleated red cells (Panel B, arrow) are also present.





129/80 mm Hg, the pulse 103 beats per minute, and the oxygen saturation 100% while he was breathing ambient air. The bowel sounds were hypoactive, and there was diffuse tenderness in both lower quadrants. The remainder of the ex-amination was unchanged.

The patient was transported to the emergency department at this hospital by wheelchair. On ex-amination, he appeared anxious and uncomfort-able. The abdomen was soft and nondistended, and he had discomfort on palpation in the lower quadrants. The blood levels of calcium, total protein, albumin, amylase, lipase, and lactic acid were normal, and routine toxicologic screening of the blood was negative; other test results are shown in Table 1. Radiography of the abdomen revealed a dilated colon, with findings sugges-tive of stool in the right and transverse colon to a transition point in the proximal descending colon. Computed tomography (CT) of the abdo-men and pelvis, performed after the administra-tion of contrast material, revealed a large amount of stool in the cecum and no evidence of ob-struction. He was admitted to this hospital.

A diagnostic test result was received.

Differ en ti a l Di agnosis

Dr. Lawrence S. Friedman: This 59-year-old man pre-sented with an acute illness characterized by epi-gastric pain, which was followed by more diffuse abdominal pain that worsened with eating. He also had an unusual constellation of symptoms that raises the possibility of a single underlying disease, and disorders that do not account for many of the features of this case can be easily ruled out.

Intraabdominal Causes of Acute Abdominal Pain

Acute abdominal pain has a broad differential diagnosis that includes both intraabdominal and extraabdominal causes.1 Life-threatening in-traabdominal catastrophes, such as gastrointes-tinal perforation, intestinal infarction, and a ruptured abdominal aortic aneurysm, cause ill-ness within minutes or hours and can be ruled out in this case by the length of the disease course and the lack of characteristic laboratory and imaging findings. Mesenteric ischemia without infarction can develop over a period of days, and abdominal pain that is disproportion-

ate to the level of abdominal tenderness (as in this case) may be suggestive of mesenteric ischemia without infarction, particularly when the cause is mesenteric-vein or arterial thrombosis and when features of infarction (e.g., acidosis, an elevated lac-tate dehydrogenase level, and hyperamylasemia) are absent. In this case, a diagnosis of mesenteric ischemia is difficult to reconcile with the find-ings of a new anemia without clear evidence of gastrointestinal bleeding, the hyponatremia in the absence of intestinal infarction, and the ab-sence of risk factors for mesenteric ischemia. A diagnosis of ischemic colitis in the absence of hematochezia would be unusual, and the find-ings are inconsistent with volvulus or an incar-cerated hernia. Colonic obstruction, perhaps due to a neoplasm, has been ruled out by the CT find-ings; moreover, results of a colonoscopy had been normal 3 years earlier.

Common causes of acute abdominal pain — appendicitis, diverticulitis, cholecystitis, pancre-atitis, and renal colic — as well as inflammatory bowel disease can be ruled out by the imaging and laboratory findings in this case. A bleeding peptic ulcer had been considered but was not confirmed on an upper endoscopic examination; also, the drop in hematocrit was not accompa-nied by gastrointestinal bleeding. Gastroenteri-tis was also suspected, but it was not consistent with this patient’s clinical course.

The elevated blood levels of aminotransferases raise the possibility of hepatitis, but the severe pain and associated extraintestinal and labora-tory features are not typical of the common hepatitis viruses2 or of a drug-induced hepatitis. Other infections that may involve the liver and have protean extrahepatic manifestations, such as visceral larva migrans,3 are unlikely because of the absence of eosinophilia, pneumonitis, and other characteristic features. This patient could have the complications of long-term alcohol use and the laboratory abnormalities associated with alcoholic hepatitis, but in that case, the blood level of aspartate aminotransferase would be higher than the blood level of alanine amino-transferase; also, in light of the severity of symp-toms, evidence of hepatic dysfunction would be expected. The age of the patient makes Wilson’s disease and other metabolic disorders, such as hereditary tyrosinemia, unlikely. Furthermore, the symptoms are inconsistent with nonalcoholic





fatty liver disease and the Budd–Chiari syndrome. The elevated aminotransferase levels may be a nonspecific component of a systemic process.

Extraabdominal Causes of Acute Abdominal Pain

The constellation of features suggests that an extra-abdominal cause of acute abdominal pain is most likely. Most entities in this category can be easily ruled out, because the diagnosis must explain the colonic pseudo-obstruction, the acute anemia without apparent gastrointestinal bleeding, and the acute hyponatremia, which appears to be caused by the syndrome of inappropriate secre-tion of antidiuretic hormone (SIADH).

Acute porphyria should be considered in a patient with acute, generally recurrent, severe abdominal pain that does not have a clear expla-nation.4 Features of this case that are consistent with a diagnosis of acute porphyria include se-vere neuropathic abdominal pain, nausea, stress or restlessness, pain in the arms and legs, con-stipation, colonic pseudo-obstruction, tachycar-dia, episodic hypertension, and SIADH; however, the characteristic dark urine was not present. Porphyrias are generally inherited and are caused by a deficiency in the activity of one of the en-zymes required for normal heme synthesis. They are categorized according to clinical presenta-tion (neurovisceral or cutaneous) and according to the principal source of overproduction of porphyrins and porphyrin precursors (typically, the bone marrow or the liver) (Table 2).5 Patients with an acute neurovisceral porphyria, most commonly acute intermittent porphyria, may present with colicky abdominal pain, often in the lower abdomen. Patients with hereditary coproporphyria and those with variegate por-phyria may present with either neurovisceral features or cutaneous features. Porphyria can be triggered by starvation, a negative energy bal-ance, the use of drugs or alcohol, smoking, in-fections, and other forms of stress. This patient is 59 years of age, and a first attack of porphyria at this age would be unusual. Alcohol could have precipitated an attack, but pirbuterol is not in-cluded on the American Porphyria Foundation list of drugs that provoke attacks of acute por-phyria or on other similar lists.

Causes of Dysgeusia and Basophilic Stippling

This patient could have had acute porphyria, but two findings that must be explained by the diag-

nosis are dysgeusia and basophilic stippling, and these are not known features of porphyria. Com-mon causes of dysgeusia are chemotherapeutic agents, such as cyclophosphamide and cisplatin, and other drugs, such as albuterol, histamine H1-receptor antagonists, penicillamine, metro-nidazole, and boceprevir; it is also associated with conditions caused by exposure to pesticides and other toxins, such as lead poisoning, as well as zinc deficiency and xerostomia.6 Dysgeusia is a known side effect of pirbuterol.

Basophilic stippling is a hallmark of sidero-blastic anemia and of lead poisoning, although it is not a constant feature of the latter.7 It is also seen in patients with arsenic poisoning, some thalassemias, a deficiency of erythrocyte pyrimidine 5'-nucleotidase, or thrombotic throm-bocytopenic purpura.

Dysgeusia and basophilic stippling were dis-tinct and prominent features in this case, although it is possible that nausea may have been per-ceived as altered taste. Arsenic poisoning causes a garlicky odor in the breath instead of true dysgeusia, and it is characteristically associated with severe diarrhea and cardiovascular symp-toms, findings that were not seen in this case.

Lead Poisoning

I believe the most likely diagnosis in this case is lead poisoning, which explains all the clinical, laboratory, and imaging features, including the abdominal pain (“lead colic”), nausea, dysgeusia, constipation, colonic pseudo-obstruction, joint and muscle pain, behavioral and cognitive changes, acute anemia, basophilic stippling, SIADH, and de-cline in the blood level of phosphorus (which may be due to renal phosphate wasting).8 Lead lines, or bluish pigmentation at the gum–tooth line caused by a reaction of lead with dental plaque, are not a reliable indicator of acute lead poisoning and were absent in this patient.9 Deposition of lead in bones may be seen with long-term exposure,10 as may hypertension11 and neuropsychiatric effects.12 The diagnosis of lead poisoning is confirmed by measuring the blood lead level; a level of 10 μg per deciliter or higher is considered elevated in adults.13 The level may be higher than 100 μg per deciliter in patients with acute lead poisoning, which is much less common than chronic lead poisoning. Heme syn-thesis is impaired when 5-aminolevulinic acid (ALA) dehydratase is 80 to 90% inhibited; this oc-





curs at a blood lead level of approximately 55 μg per deciliter.14 Because of the inhibition of ALA dehydratase and the overproduction of ALA, pa-tients with lead poisoning or with hereditary tyro-sinemia type 1 classically present with features that are similar to those of patients with acute porphyria.15 Indeed, plumboporphyria, a porphyria that is caused by a deficiency of ALA dehydra-tase, is named for “plumbum” (Latin for “lead”) because symptoms of the condition mimic those of lead poisoning, but plumboporphyria is rare and is generally reported in children.16 An elevated urine or blood level of ALA is often helpful in establishing a diagnosis of lead poisoning, al-though patients with lead poisoning and patients having an attack of acute porphyria would both be expected to have this laboratory abnormality. However, only patients with acute porphyria would also have an elevated porphobilinogen level.15 Free erythrocyte protoporphyrin and zinc protoporphyrin levels, which show the effect of lead on hemoglobin synthesis, can also be used as indicators of lead exposure over the preceding 3-month period.14

What was the source of lead poisoning in this case? The vast majority of cases of lead poison-ing in the United States result from workplace

exposures.17 I found it curious that little infor-mation was provided about the patient’s occupa-tional history or home situation. Several possi-bilities could account for exposure in this case, and the next step after making the diagnosis of lead poisoning would be to perform a rigorous investigation of the patient’s workplace and home to determine the possible sources of on-going lead exposure.

Dr. Eric S. Rosenberg (Pathology): May we have the third-year medical students’ diagnosis?

A Harvard Medical School student: This patient presented with acute abdominal pain, anemia, and arthralgias. The finding of a new micro-cytic anemia suggested a problem with heme synthesis. Because his iron levels were appar-ently normal, we concluded that the problem was most likely associated with the synthesis of porphyrin. Given the basophilic stippling and the acute disease, we thought the most likely diagnosis was acute lead poisoning, and our di-agnostic test would be a blood test for lead.

Dr. Rosenberg: Dr. Simmons, what was your im-pression when you evaluated this patient?

Dr. Leigh H. Simmons: The most striking features of the patient’s presentation were how his symp-toms changed and intensified daily during the

Table 2. Porphyrias.*

Type of Porphyria Enzymatic Defect Mode of InheritanceUsual Age at Onset

Major Site of Expression Major Biochemical Findings

Acute (Neurovisceral)

Acute intermittent porphyria PBG deaminase Autosomal dominant Adulthood Liver Urine: ALA < PBG

Plumboporphyria ALA dehydratase Autosomal recessive Childhood Liver Urine: ALA

Hereditary coproporphyria† Coproporphyrinogen oxidase

Autosomal dominant Adulthood Liver Urine: ALA > PBG, coproporphyrinStool: coproporphyrin

Variegate porphyria† Protoporphyrinogen oxidase

Autosomal dominant Adulthood Liver Urine: ALA > PBG, coproporphyrinStool: coproporphyrin, protoporphyrin

Cutaneous

Congenital erythropoietic porphyria

Uroporphyrinogen III cosynthase

Autosomal recessive Infancy Bone marrow

Urine and stool: coproporphyrin I

Erythropoietic protoporphyria

Ferrochelatase Autosomal dominant Infancy Liver, bone marrow

Urine: noneStool: protoporphyrin, coproporphyrin

Hepatoerythropoietic porphyria

Uroporphyrinogen III decarboxylase

Autosomal recessive Infancy Liver, bone marrow

Urine: uroporphyrin, 7-carboxylate porphyrin

Stool: isocoproporphyrin

Porphyria cutanea tarda Uroporphyrinogen III decarboxylase

Autosomal dominant or acquired

Adulthood Liver Urine: uroporphyrin, 7-carboxylate porphyrin

Stool: isocoproporphyrin

* ALA denotes 5-aminolevulinic acid, and PBG porphobilinogen.† Hereditary coproporphyria and variegate porphyria may also have cutaneous features.





week of acute illness and how ill he felt by the day of admission. I should add that his behav-ioral changes were striking. On the day of ad-mission, he was alternately crying and laughing; he was fearful that he was dying and also ex-pressing embarrassment about being ill.

My first consideration was peptic-ulcer dis-ease induced by increased alcohol consumption, but this was quickly dismissed when an upper endoscopic examination was normal.

I was perplexed by the anemia. The finding of basophilic stippling on the peripheral-blood smear seemed to be an important clue in this case. We considered the possibility of alcohol-induced sid-eroblastic anemia, but that would not have ex-plained any of the other symptoms. The baso-philic stippling, combined with the clinical presentation of anemia, joint pains, constipation, and behavioral changes, made me concerned about lead poisoning, and I ordered a blood test for lead.

Clinic a l Di agnosis

Lead poisoning.

DR . L AW R ENCE S. FR IEDM A N’S DI AGNOSIS

Lead poisoning.

Pathol o gic a l Discussion

Dr. Aliyah R. Sohani: Review of the peripheral-blood smear revealed a microcytic anemia, with coarse basophilic stippling, polychromasia, and occasional nucleated red cells (Fig. 1). The poly-chromasia and circulating nucleated red cells are suggestive of hemolysis, which was confirmed by an elevated reticulocyte count of 4.2% (corrected for the degree of anemia). Coarse basophilic stip-pling results from incomplete RNA degradation and abnormal ribosomal structure and reflects impaired hemoglobin synthesis or impaired iron incorporation into heme.18 Lead inhibits many of the enzymes active in the heme biosynthetic pathway, including ALA dehydratase, copropor-phyrinogen oxidase, and ferrochelatase, thereby leading to incorporation of zinc instead of iron into protoporphyrin IX (the immediate precursor of heme) and to accumulation of zinc-chelated protoporphyrin in erythrocytes, as reflected by the elevated level of zinc protoporphyrin.19 In

addition, lead inhibits erythrocyte pyrimidine 5'-nucleotidase; the hereditary form of this en-zyme deficiency results in a chronic hemolytic anemia, which is characterized by coarse baso-philic stippling.7,19

Hemoglobin electrophoresis showed no evi-dence of a structural hemoglobinopathy or a β-thalassemia trait, ruling out hemoglobinopathy as the cause of the microcytosis, basophilic stip-pling, and hemolysis. Testing for hereditary hemo-chromatosis was performed because of the pa-tient’s abnormal liver function and elevated transferrin saturation. The patient did not have the C282Y mutation of HFE, the mutation most clearly associated with hereditary hemochroma-tosis, but he was heterozygous for the H63D mu-tation of HFE, the less-penetrant mutation.20-22 The blood lead level was markedly elevated, at 91 μg per deciliter (reference range, 0 to 9), and the zinc protoporphyrin level was also elevated, at 425 μmol per mole of hemoglobin (reference range, <70); together, these values confirm the diagnosis of lead poisoning.

M a nagemen t

Dr. Simmons: When the blood lead level was found to be very elevated, I interviewed the patient about possible exposures to lead at home or at work. He worked from a home office, and so our attention turned to exposures at home. His part-ner’s blood lead level was 6 μg per deciliter. It was most helpful to interview the patient about habits he had that his partner did not; this led to the discovery that he had used an antique Russian cloisonné spoon to stir his coffee each morning for the past year and that he drank his coffee from an Italian glazed mug (Fig. 2). His partner did not drink from that set of mugs or use the spoon. At this point, I asked Dr. Goldman to perform an occupational and environmental as-sessment and to assist in the treatment of this patient.

Dr. Rose H. Goldman: I had the opportunity to see the patient for an initial assessment and follow-up consultation. To avoid the continued exposure to lead, we conducted a lengthy inves-tigation to determine its source. In many cases, a thorough occupational history uncovers poten-tial exposures. In this case, the patient was an interior designer and stated that he was never in a building during the renovation process, mak-ing exposure to lead from paint dust unlikely. He





lived in a high-rise building, was not renovating his own home, and did not do any arts and crafts work. He had not used any alternative or complementary medicines, such as Ayurvedic med-icines, some of which have been found to contain high levels of lead.23-25 He drank wine frequently, but he said that he drank from standard wine glasses, not special leaded glasses. He cooked with imported spices, which tested negative for lead. He and his partner ate the same food, but his partner’s blood lead level was within the ac-ceptable range, and thus the shared food was an unlikely source. Although we have not defini-tively identified the source of the lead, we are

highly suspicious of the imported hand-painted mugs and small antique teaspoon. The patient had these items tested at an outside laboratory, and he reported that testing of the spoon re-vealed that it was 50% lead and that one of the mugs was crushed up and consisted of about 1% lead. The glaze was reportedly intact on the re-maining mug (and had been intact on the mug that was crushed up), making it doubtful that lead was leaching from the mug. He continued using the mug for his coffee. It was not clear that the spoon was the source, since he used it only briefly to stir his coffee.

Dr. Simmons: Because the patient had severe symptoms of lead poisoning, we administered chelation treatment with calcium disodium EDTA for 4 days, followed by treatment with 2,3-dimercaptosuccinic acid (succimer) for an additional 14 days. His abdominal pain, consti-pation, and mental-status changes all complete-ly resolved within 2 days after the initiation of chelation treatment.

After the patient completed the treatment, the liver-enzyme abnormalities and anemia re-solved. However, we remain perplexed by a per-sistently elevated blood lead level; the level has steadily declined but has not yet normalized, and we are not sure why.

Dr. Goldman: There are several possible expla-nations for why the patient’s blood lead level has not returned to normal. These include high bone stores in equilibrium with the blood compart-ment, possible reexposure to lead from an un-identified source, or the presence of a genetic polymorphism, such as a polymorphism at the ALA dehydratase (ALAD) allele, which has in some cases been associated with alterations in the body’s response to lead exposure.

A nat omic a l Di agnosis

Microcytic anemia and coarse basophilic stip-pling that are consistent with lead poisoning.

This case was presented at the Medical Case Conference.Dr. Simmons reports receiving consulting fees from the New

England Research Institutes, and Dr. Goldman serving as a paid expert witness in legal cases related to occupational and environ-mental health. No other potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank Kathleen L. Hamilton for her help in the early man-agement of this case and Francis P. Colizzo, M.D., for his input in the diagnostic process.

A

B

Figure 2. The Mug and the Spoon.

The patient drank coffee from this hand-painted, glazed mug every morning (Panel A) and stirred his coffee with this spoon (Panel B).





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