Opportunistic Strongyloides stercoralis infection in lymphoma patients. Report of a case and review of the literature
ABSTRACT Strongyloides stercoralis is an intestinal parasite that may cause fatal opportunistic infections in immunocompromised patients. Herein is reported a patient who developed fatal disseminated strongyloidiasis 6 weeks after the initiation of chemotherapy for a large cell lymphoma of the small intestine. After reviewing the clinical and epidemiologic features of 16 other cases of disseminated strongyloidiasis in patients with malignant lymphomas, the currently available laboratory methods for the diagnosis of this parasite are outlined. Because uncomplicated infections are treatable, candidates for chemotherapy or immunosuppression with a relevant geographic history should be screened for S. stercoralis prior to the initiation of the treatment.
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Opportunistic Strongyloides stercoralis lnfection
in Lymphoma Patients
Report of a Case and Review of the Literature
ROBERT M. GENTA, MD,’ PATRICIA MILES, MD,t AND KAREN FIELDS, MD*
Strongyloides stercoralis is an intestinal parasite that may cause fatal opportunistic infections in immu-
nocompromised patients. Herein is reported a patient who developed fatal disseminated strongyloidiasis
6 weeks after the initiation of chemotherapy for a large cell lymphoma of the small intestine. After
reviewing the clinical and epidemiologic features of 16 other cases of disseminated strongyloidiasis in
patients with malignant lymphomas, the currently available laboratory methods for the diagnosis of this
parasite are outlined. Because uncomplicated infections are treatable, candidates for chemotherapy or
immunosuppression with a relevant geographic history should be screened for S. stercorulis prior to the
initiation of the treatment.
Cancer 63:1407-1411, 1989.
PPORTUNISTIC parasitic infections represent one of
patients.’ Viral and bacterial infections are readily diag-
nosed by well-established serologic and microbiologic
methods. In contrast, the diagnosis of parasites often re-
quires a high index of suspicion and the use of techniques,
which, particularly in industrialized nations, are not al-
ways routinely performed in clinical laboratories.
Strongyloides stercoralis is an intestinal nematode of
worldwide distribution frequently responsible for fatal
disseminated infections in compromised hosts.* Previ-
ously regarded as an exotic parasite limited to the tropics,
S. stercoralis is now found with increasing frequency also
in Europe and North Arneri~a.~,~
that physicians dealing with compromised patients be
aware of the unusual diagnostic problems associated with
this elusive parasite.
The current article reports on a patient who developed
rapidly overwhelming strongyloidiasis after therapy for a
the major challenges in the management of cancer
It is therefore essential
From the *Department of Pathology and Laboratory Medicine, Vet-
erans Administration Medical Center, University of Cincinnati College
of Medicine; the ?Department of Medicine, Division of Pulmonary
Medicine, University of Cincinnati Medical Center; and the +Department
of Medicine, Division of Hemathology and Oncology, University of Cin-
cinnati Medical Center, Cincinnati, Ohio.
Supported by the Medical Research Office of the Veterans Adminis-
The authors thank Saundra K. Eversole for typing the manuscript.
Address for reprints: Robert M. Genta, MD, Pathology-I 13, Veterans
Administration Hospital, 3200 Vine Street, Cincinnati, OH 45220.
Accepted for publication August 29, 1988.
large cell non-Hodgkin’s lymphoma. After a review of 16
similar cases described in the literature, we provide guide-
lines (based on our experience with s. stercoralis) for the
early detection of this parasitosis in candidates for im-
munosuppression or chemotherapy.
A 64-year-old white man was diagnosed as having large cell
non-Hodgkin’s lymphoma of the small bowel (Fig. 1) by ex-
ploratory laparotomy on August 27, 1987. He was started on
methotrexate, adriamycin, cytoxan, oncovin, prednisone, and
bleomycin (MACOP-B) on September 7, 1987.5 His last che-
motherapy was high dose methotrexate on October 8, 1987 fol-
lowed in 24 hours by outpatient leukovorin rescue. On October
12,1987 he complained of nausea, vomiting, and diarrhea. There
was concern that he had not completed the leukovorin rescue.
His heart rate was 120, blood pressure 98/40 mmHg, and chest
was clear to auscultation and percussion. His leukocyte count
was 900/mm3, Hg 6.1 mmol/l, Hct 28.6%, platelets 158,000/
mm3, 20% segmental neutrophils, 40% bands, 28% lymphocytes,
4% monocytes, 4% eosinophils, Na+ 129 mmol/l, K+ 3.4 mmol/
1, urea nitrogen 8.9 mmol/l, creatinine 71 pmol/l, and glucose
12.8 mmol/l. The patient was admitted October 13, 1987 for
treatment of dehydration and neutropenia. His physical ex-
amination was unchanged. He had a normal chest roentgeno-
gram, leukocyte count I 100/mm3, and hemoglobin 5.4 mmol/
1, with a hematocrit of 25%.
On October 14, 1987 the patient became confused and febrile.
Arterial blood gases on room air were pH 7.57, PO2 45, and
PC02 28. He was alert and cooperative and in moderate respi-
ratory distress. Heart rate was 140 to 150, systolic blood pressure
April I 1989
FIG. 1. Large cell lymphoma from the small intestine. The tissue was obtained 8 weeks prior to the patient’s death. Reevaluation of the intestinal
mucosa after S. stercoralis infection became apparent, which failed to reveal any parasites.
varied between 60 and 90 mmHg, respiratory rate was 35, and
oral temperature was 101.6’F. Skin was cool and dry with a
periumbilical petechial rash. There were bibasilar rales, the ab-
domen was soft with diminished bowel sounds, and no pedal
edema. Electrocardiogram showed sinus tachycardia and chest
roentgenogram showed diffuse infiltrates.
Prior to intubation, a nasogastric tube was placed and 2 1 of
coffee ground material was aspirated. A Swan-Ganz catheter
was placed with an initial wedge of 4 mmHg, systemic vascular
resistance of 378 dynesec-cm2 and cardiac output of 8.5 I/min.
The patient was started on pressors, received six units of packed
red blood cells with approximately 4 1 of crystalloid over the
next 24 hours, and was started on tobramycin and ticarcillin,
and 125 mg of aqueous methylprednisone every 6 hours. On
October 17, 1987 the patient was weaned off pressors over the
next 24 hours. The patient underwent bronchoscopy. Bron-
choalveolar lavage (BAL) returned bloody fluid teeming with S.
stercoralis filariform larvae (Fig. 2). Larvae were also seen in the
gastric aspirate, ascitic fluid, urine, and in a skin biopsy obtained
from the purpuric lesions on the abdomen. Thiabendazole 50
mg/kg/d by nasogastric tube was started and steroids were ta-
pered. The BAL subsequently grew Klebsiella spp. and Asper-
gillus flavus and A. furnigatus. Despite initial improvement for
several days, eradication of S. stercoralis by October 24, 1987
and FIOz of less than 40% from time of intubation, the patient
deteriorated over a 2-week period. He again became febrile, and
his leukocyte count rose to 38,000 mm3. On October 23, 1987
the patient bled through his endotracheal tube, although he had
normal coagulation studies.
His chest roentgenogram again worsened, with diffuse infil-
trates. Repeat bronchoscopy revealed diffuse hemorrhage. A. fu-
rnigatus was cultured from sputum collected on October 26,
1987 and the patient was started on intravenous amphotericin
B. The pulmonary infiltrates worsened and the patient could
not be adequately ventilated. He died October 3 1, 1987. A per-
mission for autopsy was not obtained.
Irnm unologic Studies
Serum titers of immunoglobulin G antibodies against S. ster-
coralis were measured by an enzyme-linked immunosorbant
assay (ELISA).6 The absorbance index (an arbitrary numerical
value calculated from the optical density, and linearly related
to specific antibody concentration) varied between 0.500 and
0.600. The range for noninfected controls is 0.001 to 0.298.
This patient’s ability to respond to S. stercoralis antigens was
confirmed by gel electrophoresis followed by immunoblotting,
performed as detailed elsewhere.’ His serum contained antibodies
OPPORTUNISTIC STRONGYLOIDIASIS IN LYMPHOMA
Genta et a/.
FIG. 2. Bronchoalveolar lavage from the patient. Innumerable S. stercoralis filarifom larvae and abundant red blood cells are present.
of the IgG, IgA, and IgM classes, which recognized nine, six,
and seven S. stercorulis filariform larval antigens, respectively.
In addition to our patient, 16 other cases of severe or
disseminated strongyloidiasis associated with lymphoma
have been reported (Table 1). In three patient^'^.'^ the
manifestations of strongyloidiasis (abdominal pain, diar-
rhea, vomiting, and weight loss) were the presenting
symptoms that eventually led to the diagnosis of lym-
phoma, and in one patient" both lymphoma and dissem-
inated strongyloidiasis were discovered only at autopsy.
In the remaining 1 1, including our patient, strongyloidiasis
developed after chemotherapy, which in all but two in-
cluded corticosteroids. The time from onset of chemo-
therapy to recognized disease ranged from 1 to 6 months.
In the last patient strongyloidiasis appeared more related
to cimetidine treatment rather than chemotherapy 14
years earlier. l 8 This relationship to chemotherapy, notably
corticosteroids, rather than to malignancy itself accords
with the figure of 80% on corticosteroids of all 120 reported
In uncomplicated gastrointestinal infection, the fre-
quency and severity of the symptoms is indistinguishable
from those in comparable hospital populations. However,
infections should be suspected in immigrants from tropical
areas,22 in military and others who served in such ar-
e a ~ , ~ ~ - ~ ~ and those who live or come from such endemic
areas as Southeastern United States" or Central and
Southern E~rope.~ Based on our experience with these
groups,26-28 we recommend that all candidates for im-
munosuppression or chemotherapy with a positive geo-
graphic history be tested for S. stercoralis (Table 2). When
available, serology represents a highly sensitive and effi-
cient screening m e t h ~ d . ~ - ~ ~ - ~ '
then undergo a thorough parasitologic investigation,
which should include at least three stool examinations of
specimens collected on different days. If serology is not
available, stool examination should be the first screening
step. However, such studies may be falsely negative, and
patients during chemotherapy or immunosuppression
Seropositive patients may
CANCER April 1 1989
TABLE 1. Clinical and Epidemiologic Data on 16 Patients With Lymphoma and Opportunistic S. stercoralis Infection
Age Sex Origin Steroids
Ret. cell. Sarcoma
Ret. cell. sarcoma
1 Y r
M: male; F female; Y: yes; D death; A: alive; NA: not reported.
* The highest eosinophil count reported in each patient.
t Time indicates the period elapsed between the initiation of che-
motherapy and the diagnosis of strongyloidiasis.
should be observed carefully for appearance of such gas-
trointestinal complaints as nausea, vomiting, diarrhea, or
abdominal pain; serpiginous skin lesions; eosinophilia; or
pulmonary infiltrates. In the last case the diagnosis may
be made by examination of sputum, bronchial washings,
The only effective treatment presently available for 5 ’ .
stercoralis is thiabendazole. At the standard dose of 50
mg/kg per day for 2 days, it has a cure rate close to 80%
in immunocompetent patient^,^' but the infection is often
difficult to eradicate in immunocompromised individu-
a l ~ . ’ ~ , ~ ~ Even when diagnosed early and treated aggres-
sively, disseminated strongyloidiasis has an overall mor-
tality rate of over 60%. The lymphoma patients discussed
here had an even worse prognosis, with only three of 17
TABLE 2. Diagnosis of Strongyloidiasis
Residence in endemic area (tropical or
subtropical countries, Southeastern USA,
Central and Southern Europe)
Eosinophilia (60% to 90% of patients)
Elevated total serum IgE (50% to 70% of
Demonstration of larvae in:
ELSA for parasite-specific IgG or IgA
(sensitivity: 85% to 90%)
Indirect immunofluorescence for parasite-
specific IgG (sensitivity: +85%)
4 These patients received cimetidine.
6 Manifestations of strongyloidiasis preceded the diagnosis of lym-
(1 8%) being successfully treated (Table 1). Most patients
die of bacterial infections associated with the larval in-
vasion of bloodstream and distant organs; respiratory
failure, often with extensive intraalveolar hemorrhage, is
also a frequent cause of death in these patients.’9320
Effective prevention of this often fatal opportunistic
infection is possible. It rests on the diagnosis and eradi-
cation of the parasite before the initiation of immuno-
suppressive or chemotherapic treatment, followed by
careful monitoring for the appearance of suggestive clin-
ical signs or laboratory abnormalities.
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