Case 3-2020: A 44-Year-Old Man With Weight Loss, Diarrhea, and Abdominal Pain

The n e w e ng l a n d j o u r na l of m e dic i n e
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 From the Department of Medicine, Bos
diarrhea, weight loss, and abdominal pain. ton Medical Center (R.C.L.), the Depart
ment of Medicine, Boston University
Approximately 6 months before admission, the patient began to have early School of Medicine (R.C.L.), the Depart
satiety, nausea approximately 30 minutes after eating small amounts of food, and ments of Medicine (J.N.C., A.A.W.), Radi
intermittent anorexia. He began to consume primarily liquids for breakfast and ology (T.T.P.), and Pathology (J.A.B.),
Massachusetts General Hospital, and
lunch and would skip dinner; during the next 5 months, he lost 9 kg. the Departments of Medicine (J.N.C.,
One month before admission, the patient was admitted to another hospital A.A.W.), Radiology (T.T.P.), and Pathol
because of fever, malaise, neck pain, photophobia, retro-orbital pain, and head- ogy (J.A.B.), Harvard Medical School —
all in Boston.
ache. 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 N Engl J Med 2020;382:365-74.
DOI: 10.1056/NEJMcpc1913473
(reference range, 4500 to 10,800); other laboratory test results are shown in Ta- Copyright © 2020 Massachusetts Medical Society.
ble 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 dexametha-
sone 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 (ref-
erence 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 hemop-
tysis 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 January 23, 2020 365

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Table 1. Laboratory Data.*
1 Mo before 3 Wk before
Current Current
Admission, Admission, Day
Reference Range, on Admission, before Discharge, Reference Range, On Admission,
Variable Other Hospital Other Hospital Other Hospital This Hospital† This Hospital
Hemoglobin (g/dl) 14.0–18.0 12.3 12.4 13.5–17.5 13.2
Hematocrit (%) 42.0–52.0 37.4 37.8 41.0–53.0 40.6
White-cell count (per μl) 4500–10,800 28,600 10,300 4500–11,000 11,170
Differential count (%)
Neutrophils 40.0–80.0 63.9 35.9 40–70 53.4
Bands 0.0–10.0 16.8
Immature granulocytes 0.7 0–0.9 0.5
Lymphocytes 7.0–36.0 5.0 43.3 22–44 29.5
Atypical lymphocytes 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
Basophils 0–1 0.5 0.6 0–1 0.4
Metamyelocytes 0.0–2.0 3.4 0
Platelet count (per μl) 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) 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
Alkaline phosphatase (U/liter) 40–129 62 53 45–115 68
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.
366 n engl j med 382;4 nejm.org January 23, 2020

Case Records of the Massachuset ts Gener al Hospital
electrophoresis were normal; other laboratory domen was soft and nondistended, with no or-
test results obtained the day before discharge ganomegaly. There was mild epigastric tender-
are shown in Table 1. ness, without rebound or guarding. No rashes,
After the patient’s discharge from the other skin ulcerations, or lymphadenopathy were noted.
hospital, new, near-constant epigastric pain de- The remainder of the examination was normal.
veloped. Approximately 1 hour after meals, nausea The international normalized ratio and blood
and vomiting occurred, with diffuse abdominal levels of magnesium, phosphorus, lipase, vita-
bloating and cramping. In addition, watery diar- min B12, folate, globulin, and IgA were normal,
rhea began to occur twice daily, without hema- as were the results of a urinalysis; other labora-
tochezia or melena. One week after discharge, tory test results are shown in Table 1. An elec-
the patient’s primary care physician prescribed trocardiogram showed right bundle-branch block,
omeprazole. The patient lost an additional 14 kg. with no evidence of ischemia.
Approximately 3 weeks later, he presented to the Dr. Theodore T. Pierce: A CT scan of the abdo-
emergency department of this hospital for evalu- men and pelvis (Fig. 1), obtained after the ad-
ation. ministration of intravenous contrast material,
The patient’s medical history was notable for showed diffuse mild distention of the large and
depression, lumbar pain, and vitamin D defi- small bowel without a transition point to indi-
ciency. Intermittent diffuse headache persisted cate a bowel obstruction. The presence of dif-
in the 3 weeks after discharge from the other fuse mild thickening of the bowel wall, mural
hospital, and the patient reported low-grade fe- enhancement, and prominent mesenteric vessels
ver. A review of systems was negative for night suggested diffuse inflammation. Additional non-
sweats, chills, neck pain, photophobia, vision specific findings included a reduced number of
changes, chest pain, dyspnea, cough, coryza, jejunal folds and an increased number of ileal
sore throat, oral ulcers, back pain, dysuria, hema- folds (collectively known as jejunoileal fold pat-
turia, rashes, joint or muscle pain, edema, and tern reversal) as well as mesenteric lymphade-
pruritus. Medications included venlafaxine, cho- nopathy.
lecalciferol, and omeprazole. The patient took an Dr. Chu: Normal saline was administered in-
herbal supplement of unknown type in the week travenously, and sucralfate and dicyclomine were
after discharge from the other hospital. He had given orally. The patient was admitted to this
never used nonsteroidal antiinflammatory drugs. hospital.
He had no known medication allergies. Diarrhea and abdominal pain persisted on the
The patient grew up on an island in the Carib- second hospital day. Tests for human immuno-
bean and had immigrated to the United States deficiency virus (HIV) type 1 and type 2 antibod-
10 years earlier; he had last returned to the ies and antigen, Treponema pallidum antibodies,
Caribbean 4 months before admission. He had Clostridium difficile antigen, and tissue transglu-
traveled extensively in the northeastern and taminase IgA were negative. Blood testing for
Mountain West regions of the United States. He Helicobacter pylori IgG was positive; however, a
was married with one child but had no known stool test for H. pylori antigen was negative.
sick contacts. He drank one beer per day and Additional diagnostic tests were performed.
had never smoked cigarettes; he occasionally
smoked marijuana. There was no family history Differ en t i a l Di agnosis
of gastrointestinal infections, gastrointestinal
cancers (his mother had ovarian cancer), peptic- Dr. Robert C. Lowe: This 44-year-old man presents
ulcer disease, pancreatitis, irritable bowel syn- with a subacute gastrointestinal illness that is
drome, inflammatory bowel disease, autoim- characterized by epigastric pain, vomiting, diar-
mune conditions, or malabsorption syndromes. rhea, and progressive weight loss during a
The temperature was 37.2°C, the heart rate 6-month period, with an intercurrent episode of
107 beats per minute, the blood pressure neutrocytic, culture-negative meningitis. Labora-
101/57 mm Hg, and the oxygen saturation 99% tory findings are notable for marked hypoalbu-
while the patient was breathing ambient air; the minemia, elevated levels of inflammatory mark-
body-mass index (the weight in kilograms divided ers, an elevated fecal calprotectin level, and a
by the square of the height in meters) was 18.6. fluctuating absolute eosinophil count that ap-
Examination was notable for cachexia. The ab- proaches the threshold for eosinophilia (1500 cells

A B
C D
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 likely, given the diffuse nature of the intestinal
only marked hyperemia of the small bowel and abnormality seen on CT imaging; nevertheless,
evidence of mesenteric lymphadenopathy. This we need to consider the possibility of lympho-
case raises several diagnostic possibilities, includ-
ma. The gastrointestinal tract is the most com-
ing cancer, autoimmune disease, and infection. mon 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

small-bowel lymphoma accounts for most cases. several extraintestinal manifestations, but neuro-
This patient has evidence of H. pylori infection, logic syndromes have not been described.3
which may contribute to lymphoma involving the Eosinophilic gastroenteritis is a rare inflam-
mucosa-associated lymphoid tissue of the stom- matory disorder of the gastrointestinal tract in
ach. The Mediterranean variety of small-bowel which eosinophilic infiltration of the mucosa of
lymphoma, known as immunoproliferative small the stomach and small bowel leads to abdomi-
intestinal disease, may be manifested by ab- nal pain, nausea, vomiting, and watery diarrhea,
dominal pain, diarrhea, malabsorption, and with weight loss occurring in a minority of pa-
weight loss. The other small-bowel lymphomas tients. In some cases, the muscular layers of the
include enteropathy-associated T-cell lymphoma gastrointestinal tract are involved, leading to gut
(associated with celiac disease), Burkitt’s lym- dysmotility and obstructive symptoms. Serosal
phoma, and B-cell lymphomas other than im- disease manifesting as ascites may also occur.
munoproliferative small intestinal disease.1 Most Peripheral eosinophilia occurs in up to 80% of
often, these tumors are associated with obstruc- patients with eosinophilic gastroenteritis, and
tion, perforation, or hemorrhage, and although imaging studies may show wall thickening of
they can be associated with more subtle muco- the gastric antrum and small bowel. The diag-
sal disease, the extent of this patient’s bowel nosis of this condition is made by examination
abnormality makes these diagnoses unlikely. of endoscopic biopsy specimens, which show
Lymphomas may also involve the meninges, but eosinophilic infiltration of the gut wall.4 This
a neutrocytic meningitis that resolves after anti- patient does not have persistent absolute eosino-
biotic therapy is not a feature of lymphomatous philia, which makes this diagnosis unlikely.
meningitis.
Infection
Autoimmune Disease Many HIV-associated infections can cause a pro-
Celiac disease, which can cause a subacute syn- longed diarrheal syndrome with weight loss, and
drome of diarrhea and weight loss as well as the presence of diffuse bowel abnormality and
hypoalbuminemia and evidence of mucosal hy- mesenteric lymphadenopathy on CT imaging in
peremia on imaging, is a consideration in this this patient is consistent with Mycobacterium
case. This patient had a negative tissue transglu- avium complex infection. However, this patient’s
taminase IgA test, but the total IgA level is not HIV screening test was negative, which rules out
reported. When considering celiac disease, it is opportunistic infections resulting from advanced
important to first rule out concomitant IgA de- HIV infection.
ficiency. If the total IgA level is low, a tissue I would be remiss if I did not raise the pos-
transglutaminase IgG test should be performed. sibility of Whipple’s disease in this case. Whip-
However, in this case, the evidence of mesen- ple’s disease may be manifested by a subacute
teric lymphadenopathy that was seen on CT and wasting illness. Infection with Tropheryma whip-
the episode of meningitis are not characteristic of plei leads to infiltration of foamy macrophages
celiac disease. Although celiac disease may have into the small bowel, which results in a syn-
neurologic manifestations, including seizures, drome of abdominal pain, diarrhea, and malab-
neuropathy, ataxia, and cognitive slowing, it is sorption that is typically accompanied by joint
not manifested by meningeal symptoms.2 pain. Other extraintestinal features include fever,
Autoimmune enteropathy is a rare disorder lymphadenopathy, and central nervous system
that can lead to subacute diarrhea and weight abnormalities, such as dementia, cerebellar atax-
loss. It is characterized by a lymphocytic im- ia, and in rare cases, oculomasticatory myorhyth-
mune reaction that causes enterocyte destruc- mia. Central nervous system involvement may be
tion and intestinal villous blunting that can manifested by mild lymphocytic pleocytosis in
mimic severe celiac disease. The presence of the CSF with an elevated total protein level. The
antienterocyte or anti–goblet-cell antibodies is diagnosis of Whipple’s disease can be made by
suggestive of this disorder, and intestinal biop- periodic acid–Schiff staining of a small-bowel
sies typically show villous blunting and evidence biopsy specimen, which would show foamy mac-
of lymphocytosis in the intestinal crypts. Auto- rophages in the lamina propria of the gut. The
immune enteropathy has been associated with organism can be identified on electron micros-

copy of biopsy specimens or with PCR testing of cades after the patient has left the region where
biopsy specimens or peripheral blood.5 The ab- the organism is endemic.7
sence of joint symptoms and the occurrence of There are several gastrointestinal manifesta-
an acute episode of neutrocytic meningitis are tions of strongyloidiasis, including epigastric
atypical for this rare disease, making it an un- pain, nausea, and vomiting, features that mimic
likely diagnosis in this case. peptic-ulcer disease. Watery diarrhea is a com-
Tropical sprue should always be considered in mon manifestation that may be accompanied by
patients from the Caribbean who present with a frank malabsorption of fat and vitamin B12.
wasting diarrheal illness. This disorder is thought Malabsorption syndrome can mimic celiac dis-
to be due to an uncharacterized intestinal infec- ease or tropical sprue and may manifest as a
tion that leads to persistent small-bowel muco- protein-losing enteropathy, characterized by hypo-
sal damage. Patients may have severe hypoalbu- albuminemia and peripheral edema.
minemia as well as diffuse bowel-wall edema Hyperinfection syndrome is associated with a
similar to that seen on this patient’s imaging greatly increased worm burden, which often oc-
studies. However, this patient has mesenteric curs in the context of immunosuppression or
lymphadenopathy, which is not a characteristic human T-lymphotropic virus type 1 (HTLV-1)
of tropical sprue. Patients with tropical sprue infection. The nematode becomes more invasive,
typically have megaloblastic anemia, which re- penetrating the bowel mucosa and causing watery
sults from both folate deficiency and vitamin B12 or bloody stools and severe abdominal pain. The
deficiency, and neutrocytic meningitis is not a worms often carry bowel flora, typically gram-
feature of this disorder. Treatment of tropical negative bacteria, through the intestinal wall,
sprue includes folate repletion and a prolonged leading to episodes of bacteremia or meningitis.
course of tetracycline.6 Although a bacterial cause can be identified in
In a patient who is from a tropical region of most cases of meningitis, neutrocytic, culture-
the world and has persistent gastrointestinal negative meningitis has been described in asso-
symptoms, parasitic infestation should also be ciation with strongyloidiasis.8
considered. A common parasitic infection that This patient is from a region in which strongy-
seems to fit with this patient’s presentation is loides is endemic, and he has a subacute wasting
strongyloidiasis with an associated hyperinfec- illness with abdominal pain, diarrhea, hypoalbu-
tion syndrome. Strongyloides stercoralis is a nema- minemia, and evidence of a diffuse small-bowel
tode that is endemic in large parts of the tropics abnormality on imaging. He has mild intermit-
and subtropics. Infection begins with inocula- tent eosinophilia and had an episode of apparent
tion of the skin with filariform larvae that reside bacterial meningitis that responded to antibiotic
in the soil. The larvae migrate through the skin therapy. His transient episodes of hemoptysis
into the bloodstream, which carries them to the are consistent with the pulmonary phase of auto-
lungs. The organisms then penetrate the alveolar infection; although the chest CT report does not
wall and ascend the bronchi and trachea until support this hypothesis, the eosinophilic infil-
they reach the pharynx, where they are swal- trates associated with strongyloidiasis (known
lowed and subsequently come to rest in the proxi- as the Löffler syndrome) may be transient. All
mal small bowel. The larvae mature into adult the features of this patient’s presentation are
worms that inhabit the mucosa of the gut, where consistent with strongyloidiasis with hyperinfec-
they shed eggs that hatch into rhabditiform lar- tion syndrome. Although the patient is not
vae that are eventually excreted in the stool. known to be immunosuppressed, he may have
A well-known characteristic of strongyloides acquired HTLV-1 infection, which would contrib-
is that it can complete its life cycle within the ute to the hyperinfection cascade. To establish
human host. In this autoinfection cycle, the this diagnosis, I would begin his workup with a
rhabditiform larvae mature into invasive filari- stool examination for rhabditiform larvae; if the
form larvae in the small bowel and colon and examination is negative, I would perform esoph-
then burrow through the bowel wall or perianal agogastroduodenoscopy as well as a duodenal
skin to restart the life cycle within the same biopsy to look for mucosal infestation with this
host. In this way, the infection can last for de- parasite.

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 villi. We obtained biopsy specimens throughout

the upper and lower gastrointestinal tract.
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. John A. Branda: Histologic examination of the
biopsy specimens of the gastrointestinal mucosa
Dr. Chu: Our differential diagnosis included stron- revealed moderately active gastritis, duodenitis, il-
gyloidiasis, celiac disease, tropical sprue, giardia eitis, and colitis, along with abundant nematodes
infection, Whipple’s disease, inflammatory bowel and ova diagnostic of strongyloidiasis (Fig. 3). A
disease, eosinophilic gastroenteritis, and micro- stool examination for ova and parasites was also
scopic colitis. To assess for these conditions, we positive for a moderate amount of S. stercoralis
performed upper and lower endoscopy (Fig. 2). rhabditiform larvae (Fig. 4). Separately, a blood
On the upper endoscopy, diffuse edema and enzyme-linked immunosorbent assay for HTLV-1
subepithelial hemorrhages were noted through- and HTLV-2 IgG was reactive, and an immunoas-
out the stomach (Fig. 2A) and duodenum say for HTLV-1 and HTLV-2 showed seroreactiv-
(Fig. 2B), and diffuse edema and small erosions ity with a band pattern that met the criteria for
were present throughout the colon (Fig. 2C). The HTLV-1 infection. Thus, the final diagnosis was
terminal ileum (Fig. 2D) had a notable loss of strongyloidiasis with HTLV-1 coinfection.

Figure 4. Stool Preparation.

B 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.
adult worm or larvae out of the intestinal lumen.

For this reason, culture-negative bacterial men-
ingitis in an otherwise healthy adult who has not
had intracranial interventions should arouse sus-
picion for strongyloidiasis. In this case, it is
likely that meningitis was a consequence of
strongyloidiasis due to transient bacteremia from
Figure 3. Biopsy Specimen of the Duodenum.
migrating organisms. Although meningitis can
Hematoxylin and eosin staining of a duodenalbiopsy
also be caused by bacterial contamination from
specimen shows dense inflammatory infiltrates involv
ing the lamina propria, with prominent eosinophils. worm migration across the blood–brain barrier,
The crypt epithelium contains Strongyloides stercoralis this situation is rare and typically occurs in pa-
ova (Panel A, arrows), larvae (Panels A and B, arrow tients with disseminated infection in whom the
heads), and adult worms (Panel B, arrows). The mor burden of nematodes can be found in many or-
phologic features and the simultaneous presence of
gans. This patient’s presentation is more typical
ova, larval nematodes, and adult nematodes in the mu
cosal tissue are diagnostic of S. stercoralis infection. of hyperinfection with severe single-organ intes-
tinal disease than of classic disseminated stron-
gyloidiasis, which usually manifests as multi-
Discussion of M a nagemen t organ dysfunction due to widespread tissue
infiltration by rhabditiform larvae.
Dr. Ana A. Weil: S. stercoralis is a nematode that The severity of symptoms is closely related to
causes strongyloidiasis, which can be asymp- the patient’s cell-mediated immune status. In this
tomatic or manifested by a range of symptoms, case, infection with HTLV-1 is the patient’s most
including shock. Mild infections are most likely important risk factor, because HTLV-1 increases
to be characterized by nonspecific gastrointesti- both the likelihood of strongyloidiasis and the
nal symptoms or incidentally identified periph- severity of disease.9,10 Studies indicate that periph-
eral eosinophilia. Among patients with a high eral-blood mononuclear cells of patients with
burden of disease, pulmonary, gastrointestinal, HTLV-1 infection produce a higher amount of
and skin symptoms can be present, and infec- γ-interferon and a lower amount of polyclonal,
tions such as bacteremia and meningitis with parasite-specific IgE than the amounts produced
enteric organisms can occur owing to transloca- in patients without HTLV-1 infection,11,12 which
tion of bacteria enabled by migration of the may result in decreased immunologic control of

infection among HTLV-1–infected patients. Among ripheral eosinophilia, more than half will have a
patients with hyperinfection, such as this pa- parasitic infection, and strongyloides is a com-
tient, and especially among those with dissemi- mon culprit.18 In general, we suggest testing for
nated disease with organ infiltration due to strongyloidiasis in persons who have geographic
widespread organisms, peripheral eosinophilia risk factors and present with peripheral eosino-
is often absent.13 Additional risk factors that in- philia or symptoms involving the gastrointesti-
crease the likelihood of strongyloidiasis include nal or respiratory system or the skin. Hyperinfec-
glucocorticoid use and other forms of immuno- tion or disseminated disease should be included
suppression that result in decreased cell-mediated in the differential diagnosis in persons who are
immunity. In this patient, the administration of from areas in which strongyloides is endemic
glucocorticoids, although brief, is likely to have and who present with unexpected infections in-
contributed to the overall nematode burden and volving enteric pathogens, especially in combi-
consequent symptoms. nation with symptoms involving the skin or re-
Treatment options for strongyloidiasis have spiratory or gastrointestinal tract. Suspicion of
not been well studied. As with many neglected hyperinfection or disseminated disease would be
tropical diseases, clinical trials are small and are increased in persons from areas in which HTLV-1
rarely conducted. For uncomplicated infection, is endemic or in persons in whom immunosup-
the Centers for Disease Control and Prevention pressive therapy, particularly glucocorticoids,
recommends a weight-based dose of ivermectin is used.
(200 μg per kilogram of body weight), adminis- Dr. Chu: Because of the severity of this pa-
tered once daily for 1 or 2 days.14 Persistent tient’s presentation, he was treated with ivermec-
symptoms after ivermectin treatment should tin (200 μg per kilogram per day) for 14 days,
arouse suspicion for treatment failure. Although followed by tapering doses every 2 weeks for
declining serologic titers may be reassuring and 1 month. He continued to receive monthly treat-
indicative of cure, quantitative serologic tests are ment with ivermectin thereafter, given that he
not widely available.15 For hyperinfection or dis- was infected with HTLV-1 and had a high risk of
seminated disease, treatment with ivermectin at persistent and recurrent infection. Serial stool
a daily dose of 200 μg per kilogram is recom- evaluation was negative. His gastrointestinal
mended, at least until stool examinations are symptoms resolved completely, and he gained
negative and symptoms are resolved; repeat ex- back more than 23 kg over the course of several
amination of the stool is recommended there- months after he began treatment.
after to test for relapse.16 Because persons who
have compromised cell-mediated immunity, in- Pathol o gic a l Di agnosis
cluding those with HTLV-1 infection, are at risk
for treatment failure, continued monitoring of Strongyloidiasis with human T-lymphotropic virus
these patients is recommended.17 type 1 infection.
A high suspicion of disease is critical for This case was presented at the Medical Case Conference.
Dr. Lowe reports receiving fees for serving as a reviewer from
reaching a diagnosis of strongyloidiasis, espe- GI Reviewers; and Dr. Branda, receiving grant support from
cially considering the high prevalence of the Zeus Scientific, bioMérieux, and Immunetics, and consulting fees
condition in many areas of the world. For exam- from T2 Biosystems, DiaSorin, and Roche Diagnostics. No other
potential conflict of interest relevant to this article was reported.
ple, among newly arrived refugees to the United Disclosure forms provided by the authors are available with
States who are found to have asymptomatic pe- the full text of this article at NEJM.org.
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Case 3-2020: A 44-Year-Old Man With Weight Loss, Diarrhea, and Abdominal Pain

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Case 3-2020: A 44-Year-Old Man with

Pr e sen tat ion of C a se

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Table 1. Laboratory Data.*

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Figure 1. CT Scan of the Abdomen and Pelvis.

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Figure 2. Upper and Lower Endoscopic Images.

Dr . Rober t C . L ow e’s Di agnosis villi. We obtained biopsy specimens throughout

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Figure 4. Stool Preparation.

adult worm or larvae out of the intestinal lumen.

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