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Case Records of the Massachusetts General Hospital

Founded by Richard C. Cabot
Eric S. Rosenberg, M.D., Editor
Jo-Anne O. Shepard, M.D., Associate Editor
Sally H. Ebeling, Assistant Editor

Nancy Lee Harris, M.D., Editor

Alice M. Cort, M.D., Associate Editor
Emily K. McDonald, Assistant Editor

Case 29-2015: A 38-Year-Old Pregnant

Woman with Headache and Visual Symptoms
Steven K. Feske, M.D., Marcia Goldberg, M.D., David M. Dudzinski, M.D.,
Ramon Gilberto Gonzalez, M.D., and Alexandra E. Kovach, M.D.

Pr e sen tat ion of C a se

From the Department of Neurology,
Brigham and Womens Hospital (S.K.F.);
the Divisions of Infectious Diseases (M.G.)
and Cardiology (D.M.D.) and the Departments of Radiology (R.G.G.) and Pathology (A.E.K.), Massachusetts General Hospital; and the Departments of Neurology
(S.K.F.), Medicine (M.G., D.M.D.), Radiology (R.G.G.), and Pathology (A.E.K.),
Harvard Medical School all in Boston.
N Engl J Med 2015;373:1154-64.
DOI: 10.1056/NEJMcpc1404335
Copyright 2015 Massachusetts Medical Society.


Dr. Blair Wylie (Obstetrics and Gynecology): A 38-year-old pregnant woman (gravida 2,
para 0) was admitted to this hospital at 33 weeks 3 days of gestation because of
headache and visual symptoms.
The patient had been in her usual health until 2 weeks before admission, when
neck pain developed. Eleven days before admission, she was seen in the emergency department and the labor and delivery unit because of neck and back pain,
occipital headache, vomiting, and a self-reported temperature of 38.9C. On examination, the back was tender; the vital signs and remainder of the examination were
normal. Laboratory test results are shown in Table 1. Urinalysis revealed yellow,
cloudy urine, with trace ketones, 1+ albumin, and 2+ urobilinogen; urine sediment
showed a few squamous cells per high-power field and mucin. Hydromorphone
and cyclobenzaprine were administered, with some improvement. The patient was
discharged home. A urine culture grew abundant mixed bacteria, with small
amounts of two potential pathogens. The headache improved spontaneously after
3 days.
On the day of presentation, the patient felt the onset of a panic attack followed
by tunnel vision; she began to hyperventilate and her vision went black from the
periphery to the center. The symptoms lasted for approximately 2 minutes and were
followed by spots in her visual fields, headache, neck pain that radiated to her
arms, nausea, and dizziness (both unsteadiness and vertigo). The capillary glucose
level, which was obtained by the patient, was 122 mg per deciliter (6.8 mmol per
liter). She called her caregivers and was advised to go to the labor and delivery unit.
On presentation, the patient reported normal fetal movement and no fever,
diarrhea, abdominal pain, vaginal bleeding, leaking fluid, or contractions. She had
received prenatal care, including screenings for syphilis, human immunodeficiency virus, gonorrhea, and chlamydia (all of which were negative) and routine
ultrasound examinations. During the third trimester, a glucose-tolerance test was
positive. She had intermittent atypical chest pain that had lasted for several years;
2.5 months before admission, an evaluation of the pain included electrocardiography (ECG), which revealed nonspecific ST-segment and T-wave changes, and transthoracic echocardiography, which was normal. At 17 years of age, she had presented
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Table 1. Laboratory Data.*

Range, Adults


6 Mo before 11 Days before



Day 3

Hematocrit (%)






Hemoglobin (g/dl)
































White-cell count (per mm3)

Differential count (%)

Platelet count (per mm3)

Mean corpuscular volume (m3)
Erythrocyte count (per mm3)
Erythrocyte sedimentation rate (mm/hr)















Sodium (mmol/liter)





Potassium (mmol/liter)





Chloride (mmol/liter)





Carbon dioxide (mmol/liter)





Glucose (mg/dl)





Albumin (g/dl)






















Urea nitrogen (mg/dl)

Creatinine (mg/dl)
Estimated glomerular filtration rate
(ml/min/1.73 m2)
Alkaline phosphatase (U/liter)
Aspartate aminotransferase (U/liter)
Alanine aminotransferase (U/liter)
Lactate dehydrogenase (U/liter)
C-reactive protein (mg/liter)









Fibrinogen (mg/dl)



Triglycerides (mg/dl)



Cholesterol (mg/dl)

<200 (desirable)


High-density lipoprotein (mg/dl)



Low-density lipoprotein (mg/dl)

<130 (desirable)




Functional protein S (%)



Free protein S antigen (%)



Cardiac risk ratio

* To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for urea nitrogen to
millimoles per liter, multiply by 0.357. To convert the values for creatinine to micromoles per liter, multiply by 88.4. To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for cholesterol to millimoles per liter, multiply by 0.02586.
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. For normal ranges in pregnancy,
see Cunningham.1
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at 20 weeks of gestation with sepsis and a stillborn fetus; dilation and evacuation had been
performed. She also had anemia (Table 1) (with
a history of iron deficiency), bipolar disorder,
panic attacks associated with syncope and tingling on the left side, recurrent pelvic pain with
pelvic adhesions, benign ovarian cysts, asthma,
and seasonal allergic rhinitis; she had had a positive purified protein derivative skin test with a
normal chest radiograph, which had been treated with isoniazid and vitamin B6 for 9 months.
She had undergone multiple laparoscopies, including cholecystectomy for cholelithiasis, lysis of adhesions, and ovarian cystectomies. Medications
included a prenatal multivitamin and ferrous sulfate; antidepressants were discontinued by the
patient at the start of the current pregnancy. She
was allergic to loperamide, morphine (which
caused chest discomfort), meperidine hydrochloride (which caused hives), and contrast material
(which caused a rash). She did not smoke, drink
alcohol, or use illicit drugs. She was born in
Guatemala, had immigrated to the United States
15 years earlier, and had last visited Guatemala
3 years earlier. She lived with her boyfriend. She
had worked in an office but was currently receiving disability benefits because of her bipolar disorder. Her mother had had breast cancer and
died in her 50s.
On examination, the temperature was 35.9C,
the blood pressure 117/68 mm Hg, the pulse
104 beats per minute, and the respiratory rate
18 breaths per minute. Her abdomen was gravid,
soft, and nontender, with active fetal movements.
The fetal heart-rate tracing was reassuring. There
was no peripheral edema or abdominal tenderness. Reflexes were normal, as were the remaining general and neurologic examinations.
The capillary glucose level was 111 mg per
deciliter (6.2 mmol per liter). Blood levels of uric
acid, magnesium, calcium, phosphorus, total protein, globulin, and total and direct bilirubin were
normal; other test results are shown in Table 1.
Intravenous fluids, acetaminophen, and butalbitalacetaminophencaffeine were administered,
followed by prochlorperazine, oxycodoneacetaminophen, and diphenhydramine; the patients
condition partially improved. Magnetic resonance
imaging (MRI) of the head could not be performed because of the patients anxiety; preliminary magnetic resonance venography showed no
evidence of sinus thrombosis.
After 24 hours of observation in the labor and

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delivery unit, the patients symptoms had not

resolved, and she was admitted to the hospital.
She reported occipital headache, which she rated
at 9 on a scale of 0 to 10 (with 10 indicating the
most severe pain).
Dr. Ramon Gilberto Gonzalez: Later that day, MRI
of the head was performed without the administration of contrast material (Fig. 1A and 1B).
Diffusion-weighted images showed multiple (at
least eight) small hyperintense lesions scattered
throughout both cerebral hemispheres, in white
and gray matter; the largest lesion (7 mm in
maximal diameter) was located in the left centrum semiovale, with no evidence of associated
intracranial mass or hemorrhage. The lesions
were thought to reflect infarcts that had occurred
at least 6 hours earlier. Results of magnetic resonance angiography and venography were normal.
Dr. Wylie: Ultrasonography of the legs revealed
no evidence of deep venous thrombosis. ECG
showed sinus tachycardia at a rate of 108 beats
per minute and nonspecific ST-segment and
T-wave changes. Holter monitoring did not reveal an arrhythmia. A lumbar puncture was unsuccessful; the patient declined further attempts.
Aspirin (81 mg daily), metoclopramide, and prenatal vitamins were administered.
On the third day, the prothrombin time,
prothrombin-time international normalized ratio,
and activated partial-thromboplastin time were
normal, as were results of tests for factor VIII,
partial-thromboplastin timelupus anticoagulant,
anticardiolipin IgG and IgM antibodies, functional antithrombin III, functional protein C,
activated protein C resistance, and prothrombin
gene mutation; other test results are shown in
Table 1. Betamethasone was administered (in two
12-mg intramusclar doses 24 hours apart) to promote fetal lung maturity. An active, well-grown
fetus was seen on ultrasound examination. The
patients headache resolved. The next day, on
evaluation by ophthalmology consultants, she
reported no acute change in vision, eye pain, or
eye redness, but she did have floaters, which she
described as worms. On examination, there
was binocular horizontal diplopia (which could
be relieved with the use of corrective lenses) and
a pterygium on the left side, with no evidence of
papilledema, embolic phenomena, or vasculitis
on funduscopic examination. Testing revealed
antibodies to hepatitis A virus; screening for
hepatitis B and C viruses was negative.
Dr. Gonzalez: Repeat MRI of the head (Fig. 1C)

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Figure 1. Axial MRI Scans of the Head.

Images were obtained at the level of the centrum semiovale. A diffusion-weighted image (Panel A) shows multiple
small hyperintensities that are indicative of acute infarcts. A few of the lesions seen on the diffusion-weighted image
(Panel A, arrow) had corresponding hyperintensities on a fluid-attenuated inverted recovery image (Panel B, arrow),
but most did not (Panel A, arrowhead); these findings indicate that the infarcts had occurred at different times.
A diffusion-weighted image that was obtained 2 days later (Panel C) shows two new punctate foci of diffusion restriction
that are indicative of new acute infarctions (arrowhead).

revealed multiple foci of restricted diffusion, including a few that were new in the bilateral frontal and right occipital lobes. These findings were
thought to be consistent with multiple small
acute infarcts.
Dr. David M. Dudzinski: On the fifth day, transthoracic echocardiography (Fig. 2; and Videos 1,
2, and 3, available with the full text of this article
at revealed a hyperkinetic left ventricle without wall-motion abnormalities and with
obliteration of the left ventricular cavity during
systole. The right ventricular apex was akinetic
and aneurysmal. In both ventricles, there was
prominent accumulation of sessile, smooth-bordered endocardial material with an echodensity
that was distinctly different from that of the
myocardium; this finding was not present on
the previous echocardiogram. Thrombus in the
left ventricle would be unlikely in this case given
the diffuse accumulation of endocardial material
and the absence of global or regional dysfunction. Apical hypertrophic cardiomyopathy could
produce a hyperkinetic ventricle with obliteration
of the left ventricular cavity during systole but
not one in which the wall has an echodensity
that is different from that of the myocardium.
Thus, the findings were suggestive of endocardial deposits. There was no patent foramen ovale
or clinically significant valvulopathy (specifically
no valvular thickening, vegetations, tethering, or
malcoaptation) and only trace mitral and tricuspid
n engl j med 373;12

regurgitation. Tissue Doppler echocardiography,

Doppler assessment of the transmitral flow velocity and pulmonary-vein flow velocity, and assessment of the color M-mode propagation velocity
revealed that the left ventricular diastolic function was normal.
Dr. Wylie: Consultations with the infectious
diseases, hematology, and rheumatology services
were requested. The level of lipoprotein(a) was
normal, and testing was negative for antibodies
to 2-glycoprotein 1, SSA (Ro), SSB (La), Sm, and
RNP and for IgG antibodies to cyclic citrullinated
peptides. A continuous intravenous infusion of
heparin was initiated. Additional diagnostic tests
were performed.

Videos showing
are available at

Differ en t i a l Di agnosis
Dr. Steven K. Feske: This woman, who was in the
third trimester of pregnancy, presented with
multiple neurologic symptoms and had lesions
on MRI that were suggestive of multiple strokes.
I will begin by reviewing the neurologic presentation and the questions it raises. Eleven days before
admission, she was evaluated for neck pain and
subjective fever. On the day of admission, she had
a 2-minute spell that was suggestive of a panic
attack, to which she is predisposed, with hyperventilation, dimming of peripheral vision, headache, neck pain, and dizziness that was specified as both unsteadiness and vertigo.

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Headache in Pregnancy

Although the majority of headaches are benign,

the combination of headache, neck pain, and
fever raises the question of infection or inflammation of the central nervous system. During
late pregnancy, one must consider preeclampsia
and eclampsia with hypertensive encephalopathy, cerebral venous sinus thrombosis, and hemorrhage as possible causes of headache. Respiratory alkalosis and hypocapnia that are due to
hyperventilation may cause light-headedness and
visual symptoms. Although visual loss may also
be caused by dysfunction in any of the structures
in the visual pathways from the retina to the
visual cortex, the transient symptoms in this
case are nonspecific and cannot be distinguished
from the effect of hyperventilation. Dizziness and
unsteadiness may be due to dysfunction of cerebellar and vestibular pathways but are also nonspecific. Therefore, neurologic localization based
on the transient symptoms is not at all precise.
The symptoms suggest transient dysfunction in
the brain stem and cerebellum and possibly in the
posterior hemispheres, which may have been
due to transient ischemic attacks or small
strokes. However, the absence of specificity for
transient ischemic attacks or stroke allows for
other possible interpretations.
The patients temperature and blood pressure
were normal. MRI of the head showed multiple
lesions typical of recent acute ischemic strokes,
with no evidence of posterior reversible encephalopathy, hemorrhage, or other lesions. Magnetic
resonance angiography revealed no flow abnormalities suggestive of reversible cerebral vasoconstriction or vasculitis, and magnetic resonance
venography revealed no evidence of cerebral venous sinus thrombosis. Laboratory evaluation
showed microcytic anemia, with a normal platelet count and striking elevation of the eosinophil
count. Mild hyponatremia and a decreased level
of carbon dioxide are normal in late pregnancy.
Levels of alkaline phosphatase, lactate dehydrogenase, and fibrinogen may all be elevated in late
pregnancy, but the levels in this case are slightly
higher than normal reported values. The erythrocyte sedimentation rate and C-reactive protein
level are also typically elevated in pregnancy, but
not to the degree that was seen in this case;
these findings are suggestive of an inflammatory disorder.1


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Figure 2. Transthoracic Echocardiograms.

A still image obtained in the apical four-chamber view
near end systole (Panel A) shows thickening of the midventricular and apical left ventricular walls, with obliteration of the cavity. A still image obtained in the parasternal short-axis view, below the level of the papillary
muscles, in diastole (Panel B) shows marked thickening of the left ventricular walls due to an accumulated
sessile material that has an echodensity that is distinctly different from that of the myocardium. A still
image obtained in the subcostal four-chamber view
in diastole (Panel C) shows aneurysmal dilatation of
the right ventricle and sessile, echodense deposits in
the apex.

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Ischemic Stroke in Pregnancy

Are the strokes related to the patients pregnancy?

Ischemic stroke is uncommon during pregnancy,
although there is a high relative increase after
delivery (relative risk, 8.7).2,3 The rate of both
ischemic and hemorrhagic strokes during pregnancy may be increasing,4 perhaps because of
increased rates of hypertension and heart disease. Normal pregnancy leads to changes in
hemodynamic function, vascular-wall structure
and integrity, endothelial function, and the levels
and function of procoagulant and anticoagulant
proteins that are factors associated with an increased risk of stroke.
The most common causes of pregnancy-associated ischemic stroke are cardioembolism, preeclampsia and eclampsia, and cerebral venous
sinus thrombosis. Acquired or inherited underlying hypercoagulability may exacerbate the physiologic prothrombotic state that occurs during
pregnancy. Atherosclerosis may also contribute
to the risk of stroke in patients with risk factors
for early-onset disease. The primary causes of
stroke in young patients in general are cardioembolism, arterial dissection, and drug abuse.
Many of these considerations have been ruled
out by the clinical presentation and laboratory
and imaging studies in this case. There is no evidence of eclamptic encephalopathy, cerebral
venous sinus thrombosis, arterial dissection, or
drug abuse. The low levels of functional protein S
and free protein S antigen are expected during
pregnancy and contribute to physiologic hypercoagulability, but they do not distinguish this
patient from other pregnant women. The multifocal strokes in the posterior and anterior circulations are suggestive of embolism from the heart
or from another proximal source or of multifocal small-vessel disease. Cerebral vasculitis most
typically causes small, deep infarcts, whereas the
presence of wedge-shaped infarcts that reach the
cortex is suggestive of embolism. The small infarcts seen on MRI in this case could result from
either of these causes of stroke. The echocardiogram offers critical information, but before addressing this, I will turn my attention to the

including parasitic and viral infections, druginduced and other allergic causes, and lymphoma
and other tumors. Current criteria for a diagnosis
of the primary hypereosinophilic syndrome include eosinophilia (>1500 cells per cubic millimeter) that has persisted for 6 months, the absence of secondary causes of eosinophilia, and
end-organ involvement.5,6 This patient does not
yet meet criteria for a primary hypereosinophilic
syndrome, since the eosinophilia has not been
present for 6 months and secondary causes have
not been ruled out. Damage to the heart due to
either primary or secondary hypereosinophilia
can be manifested by eosinophilic endocarditis
(Lfflers endocarditis)7 or endomyocardial fibrosis (Davies disease).8
The echocardiographic findings in this case
are typical of Lfflers endocarditis, which is characterized by arteritis that causes severe endocardial scarring, with negligible fibroelastosis and
commonly with thromboembolism. It may occur
with either primary or secondary hypereosinophilia. Many cases of helminthic infections
including schistosomiasis, trichinosis, and filariasis have been associated with either ischemic
strokes or endocarditis.9-14 The findings on MRI
suggest embolism as a likely mechanism of stroke.
ChurgStrauss eosinophilic vasculitis is another consideration. However, it is not supported
by the absence of lung, skin, and peripheralnerve involvement or by the results of magnetic
resonance angiography.
In summary, I think that this patient has Lfflers endocarditis as a result of either primary or
secondary hypereosinophilia. Might this diagnosis be related to her pregnancy, her origin in
Guatemala, or both?
Eosinophilia in Pregnancy

I will consider three possible connections of

eosinophilia to pregnancy: pregnancy-induced
dysregulation of eosinophils, pregnancy-related
immunosuppression with reactivation of latent
infection, and pregnancy-related geophagia (the
habit of eating clay or earth) as a potential
source of a new helminthic infection.
Eosinophils play a major role in the normal
physiological processes of pregnancy includEosinophilia
ing, for example, a controlled cytotoxic effect
Eosinophilia can be caused by the primary hyper- contributing to remodeling of the uterus and
eosinophilic syndromes or by secondary causes, there has been speculation that eosinophilic

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dysregulation may play a role in postpartum cardiomyopathy.15 However, I am aware of no cases

of severe blood eosinophilia that have been induced by pregnancy alone.
The immune status of pregnant women is
complex.16 Some reactivation infections, such as
herpes zoster, are more likely to occur during
pregnancy, and some immune-mediated diseases,
such as multiple sclerosis, tend to remit during
pregnancy. However, pregnancy does not typically increase susceptibility to infections. Although
there is some evidence of reactivation of protozoan and helminthic infections during pregnancy, this topic has not been studied adequately, and I will not consider it further.17
Helminthic Infection

I strongly favor the possibility that a new helminthic infection developed in this patient. She
had chronic microcytic anemia (probably due to
iron deficiency), which is a cause of pica (a craving to eat nonfood substances, such as soil, clay,
or cornstarch). The history indicates that she
had no eosinophilia 6 months before admission
and that she had not traveled to Guatemala for
3 years. These facts favor local exposure.
Most helminthic infections including those
caused by hookworms, whipworms, and threadworms are common in Latin America, and
risk of exposure reaches into the southern United
States. Furthermore, Toxocara canis and T. cati infect dogs and cats throughout the United States.
Could this patient have contracted toxocariasis
through geophagia? Could her recurrent visual
symptoms have, in fact, been cyclic manifestations of visceral larva migrans resulting from
toxocara infection? Might there still be a connection to Guatemala?
Guatemala is the hot spot in the Americas
for nematode infections. I can think of two possible connections to Guatemala, one indirect and
one direct. The indirect one is cultural. Geophagia is practiced in Guatemala and even encouraged during pregnancy as a desired nutritional
supplement. According to a tourist brochure
from the Christian shrine in Esquipulas, Guatemala, In Guatemala, eating clay tablets combines healing, devotional reminders, blessings
from Our Lord of Esquipulas, good fortune, and
pregnancy nutrition. Therefore, the patient may
have been encouraged to consume soil at home.
Furthermore, In Esquipulas, Guatemala, home
of the St. Esquipulas shrine, 5.7 million holy clay

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tablets are produced annually! The evolution of

the Christian shrine here may have Christianized clay consumption. The Roman Catholic
Church has indeed blessed medicinal clay tablets
since the earliest days of Christianity. Could a
well-meaning grandmother have sent the patient
clay tablets from the shrine of St. Esquipulas?
In summary, I believe this patient had a parasitic infection, most likely acquired through pica,
that caused hypereosinophilia, Lfflers endocarditis, and embolic strokes. The diagnostic
tests that I would perform would be a stool examination for ova and parasites, serologic testing for toxocara and strongyloides, and possibly
an endomyocardial biopsy.
Dr. Nancy Lee Harris (Pathology): Dr. Wylie, would
you tell us the thinking of the clinical team?
Dr. Wylie: Our working diagnosis was endocarditis due to the hypereosinophilic syndrome.
A number of services were consulted to consider
possible underlying causes.
Dr. Marcia Goldberg: We also thought that a
parasitic cause of the eosinophilia was most
likely. We ordered a stool examination for ova
and parasites, serologic testing for parasitic infection, and a bone marrow biopsy to rule out a
primary hypereosinophilic syndrome.

Cl inic a l Di agnosis
Embolic strokes due to Lfflers endocarditis,
which was possibly caused by parasitic infection
or, less likely, by a neoplastic process.

Dr . S te v en K . Fe sk es Di agnosis
Embolic strokes due to Lfflers endocarditis,
which was most likely caused by helminthic infection (toxocariasis), with secondary hypereosinophilic syndrome.

Pathol o gic a l Discussion

Dr. Alexandra E. Kovach: Examination of the bone
marrowbiopsy specimen revealed approximately
60% overall cellularity, which is normal for the
patients age and inconsistent with the hypercellularity that is typical of myeloproliferative
neoplasms. There was maturing trilineage hematopoiesis (Fig. 3A). The only abnormalities were
a slight increase in the eosinophil count in the
peripheral blood (13%) and a slight increase in
polyclonal plasma-cell count (3%); these are

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common, nonspecific findings that are associated with a variety of reactive conditions (Fig. 3B).
No iron was present on an iron stain. Results of
conventional karyotype analysis, fluorescence in
situ hybridization for the FIP1L1-PDGRFA rearrangement (which is seen in myeloproliferative neoplasms with eosinophilia), B-cell and T-cell
clonality testing by means of polymerase-chainreaction assay for an occult lymphoma, and
quantitative BCR-ABL testing for chronic myeloid
leukemia were all normal.
A panel of serologic tests for parasites was
performed. Enzyme-linked immunosorbent assays (ELISAs) were positive for antibodies against
trichinella (qualitative assay) and weakly positive
for antibodies against toxocara (quantitative assay); antibodies against strongyloides and taenia
(cysticercus) species were not detected. A single
stool examination for ova and parasites was
negative; examination of a single specimen, as
compared with multiple specimens, has a reported sensitivity of 91% in the microbiology laboratory of this hospital.18 Serum was also sent to
the Centers for Disease Control and Prevention
(CDC); serologic testing was positive for toxocara at a dilution of 1:64 (positive, >1:32), and
ELISA was positive for trichinella at 1.46 arbitrary units per milliliter (normal, <0.40).
The pathological diagnosis is hypereosinophilia, most likely due to parasitic infection. The
weakly positive result for toxocara may represent
cross-reactivity of trichinella antibodies with the
toxocara assay (or vice versa), and clinical correlation is required.

intensive care unit. Laboratory tests revealed

aminotransferase levels that were almost 10
times as high as the normal levels. We were
concerned that such endothelial dysfunction and
systemic involvement would confer both maternal and fetal risks of the HELLP syndrome (hemolysis, elevated liver-enzyme levels, and a low
platelet count). At this point, the patient was at
34 weeks of gestation, and the decision was
made to proceed with delivery.
Because the patient had right ventricular dysfunction, femoral arterial and venous catheters
were surgically placed in case extracorporeal
membrane oxygenation was required. A cesarean delivery was performed in the main operating
room with the patient receiving an epidural anesthetic. A viable male infant was delivered, with
a weight of 2960 g and Apgar scores of 7 and 8
at 1 and 5 minutes, respectively.

Discussion of M a nagemen t
Obstetrical Management

Dr. Wylie: In view of the likelihood that the hypereosinophilic syndrome was caused by a parasitic
infection, prophylactic ivermectin was administered to prevent strongyloides hyperinfection.
Therapy with high-dose intravenous glucocorticoids was then begun, and insulin was administered to maintain euglycemia.
Initially, delivery was deferred to avoid a preterm birth and to allow time for treatment to
improve the patients cardiac and neurologic
function and reduce the clot burden in the left
ventricle. Despite an improvement in her eosinophilia, severe headache recurred and paresthesias developed. Repeat MRI revealed new foci of
ischemia, and the patient was transferred to the
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Figure 3. Biopsy Specimen and Aspirate of Bone Marrow.

A bone marrowbiopsy specimen (Panel A, hematoxylin and eosin) shows overall normal cellularity and composition, with conspicuous eosinophils. A smear of the
bone marrow aspirate (Panel B, WrightGiemsa) shows
a slight increase in the proportions of mature eosinophils (arrows) and plasma cells (arrowhead).

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Consideration of Infections

Dr. Goldberg: The positive serologic tests strongly

suggested that a parasitic infection was the
cause of the patients illness. Considerations included infection with toxocara, trichinella, or
Strongyloides stercoralis or a combined infection.
Hookworm, which is present in New England,
is usually acquired through penetration of the
skin by larvae from contaminated soil but can
also be acquired through ingestion (Table 2).
Adult worms cause a chronic intestinal infection
that is accompanied by low-level eosinophilia
(500 to 700 cells per microliter); the level of
eosinophilia observed in this patient was higher
than would be expected with this condition.
Adult worms damage intestinal capillaries and
consume 0.03 to 0.20 ml of blood per day, causing
iron-deficiency anemia.19 Diagnosis is determined
by means of stool examination for ova and parasites, with a single examination reportedly having approximately 80% sensitivity.20 Given the
patients iron-deficiency anemia, the relatively
low sensitivity of a single stool examination, and
the normal eosinophil count that had been obtained 6 months earlier, we considered that
hookworm infection of less than 6 months duration may have contributed to her illness.
Although strongyloides is not endemic in New
England and the patient had not traveled to Guatemala recently, we were concerned about strongyloides infection. In a patient who is receiving
glucocorticoid treatment, strongyloides can cause
a potentially fatal hyperinfection syndrome, in
which larvae penetrate the bowel wall and disseminate, causing bacterial sepsis, colitis, pneumonia, meningitis, or a combination of these
conditions. Because this patient was receiving
glucocorticoids, we empirically administered ivermectin to prevent this potential complication. A
negative stool examination is only 30% sensitive
for strongyloides infection.20 An initial serologic
test for strongyloides was negative, but a repeat
serologic test that was performed 18 months
after admission was positive, raising the possibility that the patient could have had acute
strongyloidiasis at the time of admission.
Serologic testing was positive for both trichinella and toxocara. Serologic tests for helminths
can have cross-reactivity, which makes the interpretation of low-level positive results difficult.
Trichinella infection, which is acquired through
the ingestion of encysted larvae in meat, results

n engl j med 373;12


m e dic i n e

in the presence of encysted larvae in striated

muscle, which typically causes fever, muscle pain,
periorbital edema, eosinophilia, and an elevated
level of creatine kinase. In this case, the absence
of an elevated level of creatine kinase made
trichinella infection unlikely. The serologic test
result for trichinella was most likely false positive.
Toxocara species are acquired through the
ingestion of contaminated soil or infected meat;
these organisms are present in New England.
Larvae hatch in the human intestine and migrate
through the bloodstream to multiple organs,
including the liver, spleen, lungs, and eye. Symptoms commonly include wheezing, fever, hepatomegaly, and eosinophilia and occasionally include cough, urticaria, pruritus, pneumonia, and
anemia. In this case, the patient presented with
fever, anemia, and eosinophilia and later reported
generalized pruritus, but she did not have wheezing or other findings. Serologic testing was
positive at both our laboratory and the CDC,
making toxocara infection a potential cause of
the patients illness.
After the serologic test results were known,
the patient reported that she had ingested soil
from a yard near her home during her pregnancy. The details that were reported to various
caregivers differed, without a specific answer to
the question of whether soil or clay had been
sent to her from Guatemala. Nonetheless, this
exposure provided a potential source for ingestion of toxocara eggs, hookworm larvae, or both.
We considered it likely that pica led to toxocara infection and thereby caused hypereosinophilia. The patient may have also had subacute
hookworm infection that contributed to her severe iron-deficiency anemia, thus predisposing
her to pica.21-23
The treatment of choice for both toxocara and
hookworm infection is albendazole, which the
patient received. It also covers trichinella infection. Treatment of toxocara infection may also
include glucocorticoids. In this case, there were
multiple reasons to administer glucocorticoids,
including maturation of the fetal lungs, the hypereosinophilic syndrome, and potential toxocara
Albendazole and ivermectin are pregnancy
category C drugs (i.e., studies in animals suggest adverse fetal effects, but there are no wellcontrolled studies involving humans). Albendazole was administered only after the baby was

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The New England Journal of Medicine

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Relevant Aspects
of Presentation

n engl j med 373;12




One stool examination for ova

and parasites

(started on
hospital day
10, after

Two serologic
tests (at our
(started on
laboratory, dihospital day
lution of 1.09
10, after deliv[normal,
ery) and glu<1.00]; at CDC
laboratory, dilution of 1:64

Diagnostic Tests

Two serologic
Ivermectin (on
tests (initially
hospital days
negative but
5 and 6)
positive 18 mo
after admission) and one
stool examination for ova
and parasites

Absence of elevat- One serologic test Albendazole

ed creatine
(started on
kinase level
hospital day
10, after delivery) and glucocorticoids


Relevant Aspects
of Presentation

Features of This Case

* This is a pregnancy category C drug (i.e., studies in animals suggest adverse fetal effects, but there are no well-controlled studies involving humans) and is excreted in breast milk.

Serologic test and Ivermectin* (200

stool examinag/kg once
tion for ova
daily for
and parasites
2 days)

Test of creatine
Albendazole* (7.5
kinase level,
mg/kg twice
muscle biopsy,
daily for 1015
and serologic
days) or
(2.5 mg/kg
twice daily for
1015 days),
with or without

Penetration of skin Hyperinfection in

by larvae from
a patient recontaminated
ceiving glucosoil




Potential Source

Ingestion of infected pork, boar,

horse, or bear

Albendazole* (400
mg twice daily
for 5 days),
with or without


Trichinella spiralis

Serologic test

Diagnostic Tests

Penetration of skin Early transpulStool examination Albendazole*

Skin penetration
by larvae from
monary larval
for ova and
(400 mg once)
or pica
migration and
soil or ingesiron-deficiency
tion of larvae

Ingestion of con- Involvement of

taminated soil
various organs
or infected

Common Source

General Features


Toxocara canis,
T. cati


Table 2. Potential Parasitic Causes of Hypereosinophilia in this Patient.

Case Records of the Massachuset ts Gener al Hospital

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Case Records of the Massachuset ts Gener al Hospital

delivered. We thought that the administration of

ivermectin could not wait until after delivery
because of the potential risk of disseminated
strongyloides. Since albendazole is excreted in
breast milk, with uncertain consequences in
breast-fed babies, the patient was advised not
to breast-feed while she was receiving albendazole. She was discharged on the 14th hospital
day; she took a planned 3-week course of albendazole and a tapering course of glucocorticoids.
Warfarin was given for 6 months, and oral
and parenteral iron were administered for irondeficiency anemia. The eosinophilia had resolved
by the time of discharge and did not recur. The
echocardiographic abnormalities had resolved almost completely within 6 weeks after discharge,
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and more than 3 years later, the patient remains

well. Her child is healthy.

Pathol o gic a l Di agnose s

The hypereosinophilic syndrome due to parasitic infection (most likely toxocariasis) acquired
through pica, with Lfflers syndrome and cardioembolic strokes.
Iron-deficiency anemia.

This case was presented at Obstetrics and Gynecology Grand

No potential conflict of interest relevant to this article was
Disclosure forms provided by the authors are available with
the full text of this article at
We thank Drs. Michael Greene (Obstetrics and Gynecology) and
Thomas Byrne (Neurology) for help with organizing the conference.

and cardiomyopathy in an area endemic

for schistosomiasis. Am J Trop Med Hyg
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P, Ancelle T, Lejonc JL, Gherardi RK.
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4 or 5! Int J Cardiol 1991;31:348-9.
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SM. Review and hypothesis: the eosinophil and peripartum heart disease (myocarditis and coronary artery dissection)
coincidence or pathogenetic significance? Cardiovasc Res 1997;33:527-32.

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Halpern EF, Ferraro MJ. A rational approach to the stool ova and parasite examination. Clin Infect Dis 2006;42:972-8.
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Med Hyg 1966;15:1029-102.
20. Goka AK, Rolston DD, Mathan VI,
Farthing MJ. Diagnosis of Strongyloides
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associated with iron deficiency or depletion: clinical and laboratory correlates in
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