nejmcpc1913473

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Case Records of the Massachusetts General Hospital
Founded by Richard C. Cabot
Eric S. Rosenberg, M.D., Editor
Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Kathy M. Tran, M.D., Case Records Editorial Fellow
Emily K. McDonald, Tara Corpuz, Production Editors
Case 3-2020: A 44-Year-Old Man with
Weight Loss, Diarrhea, and Abdominal Pain
Robert C. Lowe, M.D., Jacqueline N. Chu, M.D., Theodore T. Pierce, M.D.,
Ana A. Weil, M.D., and John A. Branda, M.D.​​
Pr e sen tat ion of C a se
Dr. Jacqueline N. Chu: A 44-year-old man was evaluated at this hospital because of
diarrhea, weight loss, and abdominal pain.
Approximately 6 months before admission, the patient began to have early
satiety, nausea approximately 30 minutes after eating small amounts of food, and
intermittent anorexia. He began to consume primarily liquids for breakfast and
lunch and would skip dinner; during the next 5 months, he lost 9 kg.
One month before admission, the patient was admitted to another hospital
because of fever, malaise, neck pain, photophobia, retro-orbital pain, and headache. The temperature was 38.5°C, the heart rate 118 beats per minute, and the
blood pressure 94/72 mm Hg. The white-cell count was 28,600 per microliter
(reference range, 4500 to 10,800); other laboratory test results are shown in Table 1. Blood samples were obtained for culture. Computed tomography (CT) of the
head, performed after the administration of intravenous contrast material, was
reportedly normal. Empirical vancomycin, ceftriaxone, acyclovir, and dexamethasone were administered intravenously. A lumbar puncture (opening pressure not
recorded) revealed cloudy cerebrospinal fluid (CSF) with 4 red cells per microliter
and 1306 white cells per microliter, of which 83% were neutrophils (reference
value, <25%), 12% were monocytes, and 5% were lymphocytes. Gram’s staining of
the CSF revealed no organisms; the CSF protein level was 98 mg per deciliter (reference range, 15 to 45) and the glucose level was 68 mg per deciliter (3.8 mmol
per liter; reference range, 35 to 65 mg per deciliter [1.9 to 3.6 mmol per liter]).
On the third day at the other hospital, dysuria, nausea, and episodes of hemoptysis and diarrhea developed. CT of the chest and abdomen was performed after
the administration of intravenous contrast material; the results were reportedly
unremarkable. On the fifth hospital day, after CSF culture revealed no growth and
polymerase-chain-reaction (PCR) testing for herpes simplex virus types 1 and 2 was
negative, antimicrobial and glucocorticoid therapies were discontinued and the
patient was discharged home. The vitamin B12 level and results of serum protein
n engl j med 382;4
nejm.org
From the Department of Medicine, Bos­
ton Medical Center (R.C.L.), the Depart­
ment of Medicine, Boston University
School of Medicine (R.C.L.), the Depart­
ments of Medicine (J.N.C., A.A.W.), Radi­
ology (T.T.P.), and Pathology (J.A.B.),
Massachusetts General Hospital, and
the Departments of Medicine (J.N.C.,
A.A.W.), Radiology (T.T.P.), and Pathol­
ogy (J.A.B.), Harvard Medical School —
all in Boston.
N Engl J Med 2020;382:365-74.
DOI: 10.1056/NEJMcpc1913473
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365
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Table 1. Laboratory Data.*
Reference Range,
Other Hospital
1 Mo before
Current
Admission,
on Admission,
Other Hospital
Hemoglobin (g/dl)
14.0–18.0
12.3
12.4
13.5–17.5
Hematocrit (%)
42.0–52.0
37.4
37.8
41.0–53.0
40.6
4500–10,800
28,600
10,300
4500–11,000
11,170
Neutrophils
40.0–80.0
63.9
35.9
40–70
53.4
Bands
0.0–10.0
16.8
0.7
0–0.9
0.5
7.0–36.0
5.0
43.3
22–44
29.5
0
0.8
0
0
Monocytes
4.0–8.0
9.2
9.7
4–11
12.4
Eosinophils
1.0–6.0
0.8
9.8
0–8
5.0
0–1
0.5
0.6
0–1
0.4
Variable
White-cell count (per μl)
3 Wk before
Current
Admission, Day
before Discharge, Reference Range,
Other Hospital
This Hospital†
On Admission,
This Hospital
13.2
Differential count (%)
Immature granulocytes
Lymphocytes
Atypical lymphocytes
Basophils
0.0–2.0
3.4
Platelet count (per μl)
Metamyelocytes
150,000–450,000
258,000
415,000
150,000–400,000
395,000
Sodium (mmol/liter)
135–145
133
126
135–145
131
Potassium (mmol/liter)
3.3–4.5
4.0
4.6
3.4–5.0
4.3
Chloride (mmol/liter)
98–109
100
92
100–108
98
Carbon dioxide (mmol/liter)
24–32
22
23
23–32
23
Urea nitrogen (mg/dl)
0
6–19
14
11
8–25
11
Creatinine (mg/dl)
0.4–1.2
1.0
0.8
0.60–1.50
0.62
Glucose (mg/dl)
70–100
126
101
70–110
96
Calcium (mg/dl)
8.5–10.5
8.1
8.0
8.5–10.5
8.1
Total protein (g/dl)
6.0–8.5
5.3
5.4
6.0–8.3
5.2
Albumin (g/dl)
3.3–5.2
2.4
2.4
3.3–5.0
2.2
Alanine aminotransferase (U/liter)
0–40
32
17
10–55
38
Aspartate aminotransferase (U/liter)
0–37
19
12
10–40
30
40–129
62
53
45–115
68
Alkaline phosphatase (U/liter)
Total bilirubin (mg/dl)
0.2–1.2
0.3
0.2
0.0–1.0
0.2
Serum osmolality (mOsm/kg)
285–295
272
263
280–290
268
Lactate (mmol/liter)
0.5–1.9
1.9
0.5–2.2
1.2
Iron (μg/dl)
45–160
37
30–160
36
Total iron-binding capacity (μg/dl)
228–428
205
230–404
105
Ferritin (ng/ml)
20–250
82
10–200
130
Erythrocyte sedimentation rate (mm/hr)
0–13
7
C-reactive protein (mg/liter)
<8
59.2
Fecal calprotectin (μg/g)
<50
1038.8
*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 glucose to millimoles per liter, multiply by 0.05551. To convert the values for calcium to millimoles
per liter, multiply by 0.250. To convert the values for bilirubin to micromoles per liter, multiply by 17.1. To convert the values for lactate to
milligrams per deciliter, divide by 0.1110. To convert the values for iron and iron-binding capacity to 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.
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electrophoresis were normal; other laboratory
test results obtained the day before discharge
are shown in Table 1.
After the patient’s discharge from the other
hospital, new, near-constant epigastric pain developed. Approximately 1 hour after meals, nausea
and vomiting occurred, with diffuse abdominal
bloating and cramping. In addition, watery diarrhea began to occur twice daily, without hematochezia or melena. One week after discharge,
the patient’s primary care physician prescribed
omeprazole. The patient lost an additional 14 kg.
Approximately 3 weeks later, he presented to the
emergency department of this hospital for evaluation.
The patient’s medical history was notable for
depression, lumbar pain, and vitamin D deficiency. Intermittent diffuse headache persisted
in the 3 weeks after discharge from the other
hospital, and the patient reported low-grade fever. A review of systems was negative for night
sweats, chills, neck pain, photophobia, vision
changes, chest pain, dyspnea, cough, coryza,
sore throat, oral ulcers, back pain, dysuria, hematuria, rashes, joint or muscle pain, edema, and
pruritus. Medications included venlafaxine, cholecalciferol, and omeprazole. The patient took an
herbal supplement of unknown type in the week
after discharge from the other hospital. He had
never used nonsteroidal antiinflammatory drugs.
He had no known medication allergies.
The patient grew up on an island in the Caribbean and had immigrated to the United States
10 years earlier; he had last returned to the
Caribbean 4 months before admission. He had
traveled extensively in the northeastern and
Mountain West regions of the United States. He
was married with one child but had no known
sick contacts. He drank one beer per day and
had never smoked cigarettes; he occasionally
smoked marijuana. There was no family history
of gastrointestinal infections, gastrointestinal
cancers (his mother had ovarian cancer), pepticulcer disease, pancreatitis, irritable bowel syndrome, inflammatory bowel disease, autoimmune conditions, or malabsorption syndromes.
The temperature was 37.2°C, the heart rate
107 beats per minute, the blood pressure
101/57 mm Hg, and the oxygen saturation 99%
while the patient was breathing ambient air; the
body-mass index (the weight in kilograms divided
by the square of the height in meters) was 18.6.
Examination was notable for cachexia. The abn engl j med 382;4
domen was soft and nondistended, with no organomegaly. There was mild epigastric tenderness, without rebound or guarding. No rashes,
skin ulcerations, or lymphadenopathy were noted.
The remainder of the examination was normal.
The international normalized ratio and blood
levels of magnesium, phosphorus, lipase, vitamin B12, folate, globulin, and IgA were normal,
as were the results of a urinalysis; other laboratory test results are shown in Table 1. An electrocardiogram showed right bundle-branch block,
with no evidence of ischemia.
Dr. Theodore T. Pierce: A CT scan of the abdomen and pelvis (Fig. 1), obtained after the administration of intravenous contrast material,
showed diffuse mild distention of the large and
small bowel without a transition point to indicate a bowel obstruction. The presence of diffuse mild thickening of the bowel wall, mural
enhancement, and prominent mesenteric vessels
suggested diffuse inflammation. Additional nonspecific findings included a reduced number of
jejunal folds and an increased number of ileal
folds (collectively known as jejunoileal fold pattern reversal) as well as mesenteric lymphadenopathy.
Dr. Chu: Normal saline was administered intravenously, and sucralfate and dicyclomine were
given orally. The patient was admitted to this
hospital.
Diarrhea and abdominal pain persisted on the
second hospital day. Tests for human immunodeficiency virus (HIV) type 1 and type 2 antibodies and antigen, Treponema pallidum antibodies,
Clostridium difficile antigen, and tissue transglutaminase IgA were negative. Blood testing for
Helicobacter pylori IgG was positive; however, a
stool test for H. pylori antigen was negative.
Additional diagnostic tests were performed.
Differ en t i a l Di agnosis
Dr. Robert C. Lowe: This 44-year-old man presents
with a subacute gastrointestinal illness that is
characterized by epigastric pain, vomiting, diarrhea, and progressive weight loss during a
6-month period, with an intercurrent episode of
neutrocytic, culture-negative meningitis. Laboratory findings are notable for marked hypoalbuminemia, elevated levels of inflammatory markers, an elevated fecal calprotectin level, and a
fluctuating absolute eosinophil count that approaches the threshold for eosinophilia (1500 cells
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A
B
C
D
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Figure 1. CT Scan of the Abdomen and Pelvis.
A coronal reformation image (Panel A) shows prominent air­filled and fluid­filled loops of small bowel throughout
the abdomen with mural thickening and enhancement (arrows). The jejunum, located in the left upper quadrant,
lacks typical mural folds. An axial image of the pelvis (Panel B) shows dilatation of the ileum, thickening of the ileal
wall, and prominent mural folds (arrows). An axial image of the transverse colon (Panel C) shows mild thickening of
the haustral folds (arrows). An axial image of the midabdomen (Panel D) shows engorged mesenteric vessels (yel­
low dashed line) and a representative enlarged mesenteric lymph node (blue dashed line). This constellation of
findings is compatible with diffuse enterocolonic inflammation.
per microliter) but does not reach it. CT shows
only marked hyperemia of the small bowel and
evidence of mesenteric lymphadenopathy. This
case raises several diagnostic possibilities, including cancer, autoimmune disease, and infection.
likely, given the diffuse nature of the intestinal
abnormality seen on CT imaging; nevertheless,
we need to consider the possibility of lymphoma. The gastrointestinal tract is the most common extranodal site of lymphoma. In the United
States, up to 75% of cases of gastrointestinal
Cancer
lymphoma involve the stomach, whereas less
Although cancer must be included in the differ- than 10% involve the small bowel. However, in
ential diagnosis, a malignant process seems un- the Middle East and the Mediterranean, primary
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small-bowel lymphoma accounts for most cases.
This patient has evidence of H. pylori infection,
which may contribute to lymphoma involving the
mucosa-associated lymphoid tissue of the stomach. The Mediterranean variety of small-bowel
lymphoma, known as immunoproliferative small
intestinal disease, may be manifested by abdominal pain, diarrhea, malabsorption, and
weight loss. The other small-bowel lymphomas
include enteropathy-associated T-cell lymphoma
(associated with celiac disease), Burkitt’s lymphoma, and B-cell lymphomas other than immunoproliferative small intestinal disease.1 Most
often, these tumors are associated with obstruction, perforation, or hemorrhage, and although
they can be associated with more subtle mucosal disease, the extent of this patient’s bowel
abnormality makes these diagnoses unlikely.
Lymphomas may also involve the meninges, but
a neutrocytic meningitis that resolves after antibiotic therapy is not a feature of lymphomatous
meningitis.
several extraintestinal manifestations, but neurologic syndromes have not been described.3
Eosinophilic gastroenteritis is a rare inflammatory disorder of the gastrointestinal tract in
which eosinophilic infiltration of the mucosa of
the stomach and small bowel leads to abdominal pain, nausea, vomiting, and watery diarrhea,
with weight loss occurring in a minority of patients. In some cases, the muscular layers of the
gastrointestinal tract are involved, leading to gut
dysmotility and obstructive symptoms. Serosal
disease manifesting as ascites may also occur.
Peripheral eosinophilia occurs in up to 80% of
patients with eosinophilic gastroenteritis, and
imaging studies may show wall thickening of
the gastric antrum and small bowel. The diagnosis of this condition is made by examination
of endoscopic biopsy specimens, which show
eosinophilic infiltration of the gut wall.4 This
patient does not have persistent absolute eosinophilia, which makes this diagnosis unlikely.
Infection
Autoimmune Disease
Celiac disease, which can cause a subacute syndrome of diarrhea and weight loss as well as
hypoalbuminemia and evidence of mucosal hyperemia on imaging, is a consideration in this
case. This patient had a negative tissue transglutaminase IgA test, but the total IgA level is not
reported. When considering celiac disease, it is
important to first rule out concomitant IgA deficiency. If the total IgA level is low, a tissue
transglutaminase IgG test should be performed.
However, in this case, the evidence of mesenteric lymphadenopathy that was seen on CT and
the episode of meningitis are not characteristic of
celiac disease. Although celiac disease may have
neurologic manifestations, including seizures,
neuropathy, ataxia, and cognitive slowing, it is
not manifested by meningeal symptoms.2
Autoimmune enteropathy is a rare disorder
that can lead to subacute diarrhea and weight
loss. It is characterized by a lymphocytic immune reaction that causes enterocyte destruction and intestinal villous blunting that can
mimic severe celiac disease. The presence of
antienterocyte or anti–goblet-cell antibodies is
suggestive of this disorder, and intestinal biopsies typically show villous blunting and evidence
of lymphocytosis in the intestinal crypts. Autoimmune enteropathy has been associated with
n engl j med 382;4
Many HIV-associated infections can cause a prolonged diarrheal syndrome with weight loss, and
the presence of diffuse bowel abnormality and
mesenteric lymphadenopathy on CT imaging in
this patient is consistent with Mycobacterium
avium complex infection. However, this patient’s
HIV screening test was negative, which rules out
opportunistic infections resulting from advanced
HIV infection.
I would be remiss if I did not raise the possibility of Whipple’s disease in this case. Whipple’s disease may be manifested by a subacute
wasting illness. Infection with Tropheryma whipplei leads to infiltration of foamy macrophages
into the small bowel, which results in a syndrome of abdominal pain, diarrhea, and malabsorption that is typically accompanied by joint
pain. Other extraintestinal features include fever,
lymphadenopathy, and central nervous system
abnormalities, such as dementia, cerebellar ataxia, and in rare cases, oculomasticatory myorhythmia. Central nervous system involvement may be
manifested by mild lymphocytic pleocytosis in
the CSF with an elevated total protein level. The
diagnosis of Whipple’s disease can be made by
periodic acid–Schiff staining of a small-bowel
biopsy specimen, which would show foamy macrophages in the lamina propria of the gut. The
organism can be identified on electron micros-
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369
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copy of biopsy specimens or with PCR testing of
biopsy specimens or peripheral blood.5 The absence of joint symptoms and the occurrence of
an acute episode of neutrocytic meningitis are
atypical for this rare disease, making it an unlikely diagnosis in this case.
Tropical sprue should always be considered in
patients from the Caribbean who present with a
wasting diarrheal illness. This disorder is thought
to be due to an uncharacterized intestinal infection that leads to persistent small-bowel mucosal damage. Patients may have severe hypoalbuminemia as well as diffuse bowel-wall edema
similar to that seen on this patient’s imaging
studies. However, this patient has mesenteric
lymphadenopathy, which is not a characteristic
of tropical sprue. Patients with tropical sprue
typically have megaloblastic anemia, which results from both folate deficiency and vitamin B12
deficiency, and neutrocytic meningitis is not a
feature of this disorder. Treatment of tropical
sprue includes folate repletion and a prolonged
course of tetracycline.6
In a patient who is from a tropical region of
the world and has persistent gastrointestinal
symptoms, parasitic infestation should also be
considered. A common parasitic infection that
seems to fit with this patient’s presentation is
strongyloidiasis with an associated hyperinfection syndrome. Strongyloides stercoralis is a nematode that is endemic in large parts of the tropics
and subtropics. Infection begins with inoculation of the skin with filariform larvae that reside
in the soil. The larvae migrate through the skin
into the bloodstream, which carries them to the
lungs. The organisms then penetrate the alveolar
wall and ascend the bronchi and trachea until
they reach the pharynx, where they are swallowed and subsequently come to rest in the proximal small bowel. The larvae mature into adult
worms that inhabit the mucosa of the gut, where
they shed eggs that hatch into rhabditiform larvae that are eventually excreted in the stool.
A well-known characteristic of strongyloides
is that it can complete its life cycle within the
human host. In this autoinfection cycle, the
rhabditiform larvae mature into invasive filariform larvae in the small bowel and colon and
then burrow through the bowel wall or perianal
skin to restart the life cycle within the same
host. In this way, the infection can last for de-
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cades after the patient has left the region where
the organism is endemic.7
There are several gastrointestinal manifestations of strongyloidiasis, including epigastric
pain, nausea, and vomiting, features that mimic
peptic-ulcer disease. Watery diarrhea is a common manifestation that may be accompanied by
frank malabsorption of fat and vitamin B12.
Malabsorption syndrome can mimic celiac disease or tropical sprue and may manifest as a
protein-losing enteropathy, characterized by hypoalbuminemia and peripheral edema.
Hyperinfection syndrome is associated with a
greatly increased worm burden, which often occurs in the context of immunosuppression or
human T-lymphotropic virus type 1 (HTLV-1)
infection. The nematode becomes more invasive,
penetrating the bowel mucosa and causing watery
or bloody stools and severe abdominal pain. The
worms often carry bowel flora, typically gramnegative bacteria, through the intestinal wall,
leading to episodes of bacteremia or meningitis.
Although a bacterial cause can be identified in
most cases of meningitis, neutrocytic, culturenegative meningitis has been described in association with strongyloidiasis.8
This patient is from a region in which strongyloides is endemic, and he has a subacute wasting
illness with abdominal pain, diarrhea, hypoalbuminemia, and evidence of a diffuse small-bowel
abnormality on imaging. He has mild intermittent eosinophilia and had an episode of apparent
bacterial meningitis that responded to antibiotic
therapy. His transient episodes of hemoptysis
are consistent with the pulmonary phase of autoinfection; although the chest CT report does not
support this hypothesis, the eosinophilic infiltrates associated with strongyloidiasis (known
as the Löffler syndrome) may be transient. All
the features of this patient’s presentation are
consistent with strongyloidiasis with hyperinfection syndrome. Although the patient is not
known to be immunosuppressed, he may have
acquired HTLV-1 infection, which would contribute to the hyperinfection cascade. To establish
this diagnosis, I would begin his workup with a
stool examination for rhabditiform larvae; if the
examination is negative, I would perform esophagogastroduodenoscopy as well as a duodenal
biopsy to look for mucosal infestation with this
parasite.
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Case Records of the Massachuset ts Gener al Hospital
A
B
C
D
Figure 2. Upper and Lower Endoscopic Images.
Endoscopic views of the stomach (Panel A) and duodenum (Panel B) show diffuse edema and subepithelial hemor­
rhages, and diffuse edema and small erosions are seen in the colon (Panel C). The terminal ileum (Panel D) is nota­
ble for a loss of villi.
Dr . Rober t C . L ow e’s Di agnosis
Strongyloidiasis with hyperinfection syndrome.
Pathol o gic a l Discussion
Cl inic a l Impr e ssion
a nd End osc opic E va luat ion
Dr. Chu: Our differential diagnosis included strongyloidiasis, celiac disease, tropical sprue, giardia
infection, Whipple’s disease, inflammatory bowel
disease, eosinophilic gastroenteritis, and microscopic colitis. To assess for these conditions, we
performed upper and lower endoscopy (Fig. 2).
On the upper endoscopy, diffuse edema and
subepithelial hemorrhages were noted throughout the stomach (Fig. 2A) and duodenum
(Fig. 2B), and diffuse edema and small erosions
were present throughout the colon (Fig. 2C). The
terminal ileum (Fig. 2D) had a notable loss of
n engl j med 382;4
villi. We obtained biopsy specimens throughout
the upper and lower gastrointestinal tract.
Dr. John A. Branda: Histologic examination of the
biopsy specimens of the gastrointestinal mucosa
revealed moderately active gastritis, duodenitis, ileitis, and colitis, along with abundant nematodes
and ova diagnostic of strongyloidiasis (Fig. 3). A
stool examination for ova and parasites was also
positive for a moderate amount of S. stercoralis
rhabditiform larvae (Fig. 4). Separately, a blood
enzyme-linked immunosorbent assay for HTLV-1
and HTLV-2 IgG was reactive, and an immunoassay for HTLV-1 and HTLV-2 showed seroreactivity with a band pattern that met the criteria for
HTLV-1 infection. Thus, the final diagnosis was
strongyloidiasis with HTLV-1 coinfection.
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371
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A
Figure 4. Stool Preparation.
A concentrated wet preparation of stool contained
rhabditiform larvae of S. stercoralis. Characteristic
features of the larvae include a short buccal canal,
a bulbous esophagus, a prominent genital primor­
dium, and a pointed tail.
B
Figure 3. Biopsy Specimen of the Duodenum.
Hematoxylin and eosin staining of a duodenal­biopsy
specimen shows dense inflammatory infiltrates involv­
ing the lamina propria, with prominent eosinophils.
The crypt epithelium contains Strongyloides stercoralis
ova (Panel A, arrows), larvae (Panels A and B, arrow­
heads), and adult worms (Panel B, arrows). The mor­
phologic features and the simultaneous presence of
ova, larval nematodes, and adult nematodes in the mu­
cosal tissue are diagnostic of S. stercoralis infection.
Discussion of M a nagemen t
Dr. Ana A. Weil: S. stercoralis is a nematode that
causes strongyloidiasis, which can be asymptomatic or manifested by a range of symptoms,
including shock. Mild infections are most likely
to be characterized by nonspecific gastrointestinal symptoms or incidentally identified peripheral eosinophilia. Among patients with a high
burden of disease, pulmonary, gastrointestinal,
and skin symptoms can be present, and infections such as bacteremia and meningitis with
enteric organisms can occur owing to translocation of bacteria enabled by migration of the
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adult worm or larvae out of the intestinal lumen.
For this reason, culture-negative bacterial meningitis in an otherwise healthy adult who has not
had intracranial interventions should arouse suspicion for strongyloidiasis. In this case, it is
likely that meningitis was a consequence of
strongyloidiasis due to transient bacteremia from
migrating organisms. Although meningitis can
also be caused by bacterial contamination from
worm migration across the blood–brain barrier,
this situation is rare and typically occurs in patients with disseminated infection in whom the
burden of nematodes can be found in many organs. This patient’s presentation is more typical
of hyperinfection with severe single-organ intestinal disease than of classic disseminated strongyloidiasis, which usually manifests as multiorgan dysfunction due to widespread tissue
infiltration by rhabditiform larvae.
The severity of symptoms is closely related to
the patient’s cell-mediated immune status. In this
case, infection with HTLV-1 is the patient’s most
important risk factor, because HTLV-1 increases
both the likelihood of strongyloidiasis and the
severity of disease.9,10 Studies indicate that peripheral-blood mononuclear cells of patients with
HTLV-1 infection produce a higher amount of
γ-interferon and a lower amount of polyclonal,
parasite-specific IgE than the amounts produced
in patients without HTLV-1 infection,11,12 which
may result in decreased immunologic control of
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Case Records of the Massachuset ts Gener al Hospital
infection among HTLV-1–infected patients. Among
patients with hyperinfection, such as this patient, and especially among those with disseminated disease with organ infiltration due to
widespread organisms, peripheral eosinophilia
is often absent.13 Additional risk factors that increase the likelihood of strongyloidiasis include
glucocorticoid use and other forms of immunosuppression that result in decreased cell-mediated
immunity. In this patient, the administration of
glucocorticoids, although brief, is likely to have
contributed to the overall nematode burden and
consequent symptoms.
Treatment options for strongyloidiasis have
not been well studied. As with many neglected
tropical diseases, clinical trials are small and are
rarely conducted. For uncomplicated infection,
the Centers for Disease Control and Prevention
recommends a weight-based dose of ivermectin
(200 μg per kilogram of body weight), administered once daily for 1 or 2 days.14 Persistent
symptoms after ivermectin treatment should
arouse suspicion for treatment failure. Although
declining serologic titers may be reassuring and
indicative of cure, quantitative serologic tests are
not widely available.15 For hyperinfection or disseminated disease, treatment with ivermectin at
a daily dose of 200 μg per kilogram is recommended, at least until stool examinations are
negative and symptoms are resolved; repeat examination of the stool is recommended thereafter to test for relapse.16 Because persons who
have compromised cell-mediated immunity, including those with HTLV-1 infection, are at risk
for treatment failure, continued monitoring of
these patients is recommended.17
A high suspicion of disease is critical for
reaching a diagnosis of strongyloidiasis, especially considering the high prevalence of the
condition in many areas of the world. For example, among newly arrived refugees to the United
States who are found to have asymptomatic peReferences
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Dr. Chu: Because of the severity of this patient’s presentation, he was treated with ivermectin (200 μg per kilogram per day) for 14 days,
followed by tapering doses every 2 weeks for
1 month. He continued to receive monthly treatment with ivermectin thereafter, given that he
was infected with HTLV-1 and had a high risk of
persistent and recurrent infection. Serial stool
evaluation was negative. His gastrointestinal
symptoms resolved completely, and he gained
back more than 23 kg over the course of several
months after he began treatment.
Pathol o gic a l Di agnosis
Strongyloidiasis with human T-lymphotropic virus
type 1 infection.
This case was presented at the Medical Case Conference.
Dr. Lowe reports receiving fees for serving as a reviewer from
GI Reviewers; and Dr. Branda, receiving grant support from
Zeus Scientific, bioMérieux, and Immunetics, and consulting fees
from T2 Biosystems, DiaSorin, and Roche Diagnostics. 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.
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