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Eosinophilic colitis associated with larvae
of the pinworm Enterobius vermicularis
Various helmintic parasites, most of which are uncommon
in economically developed countries, can cause abdominal
pain and eosinophilic inflammation of the bowel. A
homosexual man presented with severe abdominal pain and
haemorrhagic colitis, eosinophilic inflammation of the
ileum and colon, and numerous unidentifiable larval
nematodes in diarrhoeal stool. His symptoms resolved with
anthelmintic treatment alone. Using comparative
morphology and molecular cloning of nematode ribosomal
RNA genes, we identified the parasites as larvae of the
pinworm Enterobius vermicularis, which are rarely observed
or associated with disease. Occult enterobiasis is widely
prevalent and may be a cause of unexplained eosinophilic
enterocolitis.
Lancet 1995; 346: 410-12
Various intestinal nematodes can cause abdominal pain
and enteritis, including hookworm, and species of
strongyloides, anisakis, and intestinal trichinella.’ These
infections primarily involve the small intestine and usually
cause peripheral eosinophilia due to parasitic penetration
410
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1992; 327: 765.
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585-88.
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versus placebo in symptomatic erosive esophagitis: the US Multicentre
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pain? Arch Intern Med 1986; 146: 353-56.
of mucosa. dog hookworm Ancylostoma caninum is
The
recognised as a of human eosinophilic enteritis.2
cause
Heavy infections with the colonic whipworm Trichuris
trichiura can result in a dysentery-like syndrome,.’
Infections with the common pinworm, Enterobius
vermicularis, are usually asymptomatic or cause only anal
pruritis, except for occasional ectopic migration into the
appendix or the female genital tract by adult pinworms.4
We describe a patient with haemorrhagic eosinophilic
enterocolitis associated with numerous nematode larvae,
which were identified by morphological and molecular
criteria as E vermicularis.
An 18-year-old man was admitted with a 3 day history of
abdominal pain and melena, without vomiting or fever. He had
no relevant medical history, including atopy and food allergy, did
not drink alcohol excessively, and had not recently taken aspirin
or other drugs. He was born and lived in Boston, did not own a
dog, had never travelled abroad, and was homosexual with a
single partner. He had normal vital signs, severe abdominal
tenderness in the right lower quadrant, and melenic stool. His
white cell count was 12-6xlO"/L with 77% neutrophils, 15%
lymphocytes, 5% monocytes, and 3% eosinophils. Other routine
haematological and blood chemistry test results were normal.
HIV antibody was negative. Upper endocopy findings were
normal. Colonoscopy showed purulent discharge from the
rectum to the terminal ileum, erythematous and friable mucosa,
and numerous small stellate ulcerations. Six biopsy specimens,
from rectum to ileum, revealed intense infiltration of the surface
enterocyte layer by eosinophils, and patchy ulceration with
overlying pseudomembranes composed of fibrin, neutrophils,
and, especially in the lamina propria, crypts, and capillaries,
many eosinophils. No biopsy sample revealed granulomas,
invasive microorganisms, viral inclusions, dysplasia, or extension
of inflammation below the muscularis mucosae.
Figure: PCR and nematode morphology
5S rRNA spacer of unknown nematode is identical in size (about 890 basepairs) to that of E vermicularis, and different from that of other major human
intestinal parasitic nematodes and C elegans. M=100 basepair-ladder molecular-weight marker.
Representative unknown nematode larva, length 1 mm. Oesophagus (bottom left) comprises long muscular portion, isthmus, and bulb at junction
with densely granular intestine. Tail tapers to pointed end, typical of female E vermicularis. There are no discernable reproductive organs or cephalic
inflations that would indicate adult worms.5 Magnification 2000X.
Cecal biopsy specimen showing larval pinworm sections. Nematode intestine, muscle cells, lateral chords, and lateral cuticular alae (a) are visible.
Parasagittal cuticle section of nematode (n) overlies pseudomembranous ulcerated cecal mucosa. Magnification 2000X.

Stool cultures were negative for Salmonella, Shigella,
Campylobacter, Yersinia, and Aeromonas species and for Escherichia
coli 0157:H7. A cytotoxicity assay for Clostridium difficile toxin
B was negative. Stool examination for ova and parasites revealed
about ten undifferentiated nematode larvae per mL. No helminth
eggs, adult worms, or protozoa were seen. The larvae could not
be identified during the hospital stay and were preserved in
ethanol and at -70°C. The patient was treated with
mebendazole 100 mg twice daily for 3 days. No steroids or anti-
inflammatory drugs were administered. His abdominal pain and
diarrhoea subsided during the course of mebendazole.
Subsequent stool and proctoscopic examinations were negative,
and the patient has remained free of symptoms over 18 months
of follow-up.
A molecular identification of the nematode was done by
cloning nematode 28S ribosomal RNA and 5S rRNA spacer
genes by PCR. Genomic DNA was extracted from individual
frozen larvae of the unidentified species and from other common
intestinal nematode species, and amplified with the following
oligonucleotide primers: 28S rRNA forward 5’-GGGAATTCC-
CTGAACTCAGTCGTGATTACCC-3’ ; 28S rRNA reverse,
5’-GGTCTAGAGCACTTTCAAGCAACCCGAC-3’; 5S RNA
spacer forward, 5’-GCGAATTCTTGGATCGGAGACGG-
CCTG-3’ ; and 5S rRNA spacer reverse, 5’-GCTCTAGACGA-
GATGTCGTGCTTTCAACG-3’.
The DNA sequence of about 300 basepairs of the 28S
rRNA gene target from the unknown nematode was
identical to that of a reference E vermicularis adult worm
(from an established case of pinworm infection in Los
Angeles), and differed from the 28S rRNA sequences of
other parasitic nematodes (not shown). Because the 5S
rRNA spacer region is highly divergent in size and
sequence among species, differently sized 5S rRNA
spacer PCR products were amplified from various
intestinal nematode parasites (figure). The 5S rRNA
spacer DNA sequences of the unknown nematode and
E vermicularis were identical in size (893 basepairs) and
99% identical in nucleotide sequence, which is indicative
of minor non-coding base differences between disparate
geographic isolates.
All of the nematodes recovered were immature larvae
1-0 mm in length, with a typical oxyurid oesophagus and
pointed tail characteristic of female E vermicularis
(figure).5 A molting cuticle overlying the tail indicated that
these were fourth-stage larvae in the process of the final
molt to the adult worm. Retrospective examination of
additional sections revealed a nematode overlying a
mucosal ulcer in the caecum (figure).
Abdominal pain and eosinophilic infiltration of the
bowel can occur in various conditions, including
helmintic parasitic infections, inflammatory bowel
disease, and eosinophilic gastroenteritis.6 In most
instances the cause of eosinophilic enteritis or ileocolitis

411
is never identified or is ascribed to food allergy.7
E vermicularis larvae have only rarely been described5$
with several early reports of severe colitis, with multiple
small ulcers, associated with abundant enterobius
larvae."’" All the nematodes recovered from our patient
were at an identical stage of advanced larval development,
which indicates a synchronous infection acquired 10-14
days before presentation.8 During the pinworm life cycle,
adult female worms that inhabit the caecum and proximal
colon migrate out onto the perianal skin, where they
deposit eggs. Enterobiasis is usually acquired by the oral
ingestion of infectious eggs transferred from the perianal
region directly by the fingernails (autoinfection) or via
contaminated night clothing, bed linens, or household
dust.4 However, our patient most probably directly
acquired the infection from his partner via the anal-oral
route. Such practice may account in part for the
substantial prevalence of enterobiasis among homosexual
men. Several pathogens are implicated in the "gay bowel"
syndrome, but no other bacterial or protozoal pathogens
were isolated during or after our patient’s acute course. In
addition, his history and clinical course did not support a
diagnosis of inflammatory bowel disease or food allergy.
In this case, the presence of pinworm larvae in stool and
histological examinations associated with severe colitis,
the rapid and long-term improvement with anthelmintic
treatment alone, and the historical rarity of finding
pinworm larvae all argue strongly against these larvae
being an incidental finding.
Many parasitology textbooks state that advanced
E vermicularis larvae or young adult worms may become
attached to the colon epithelium, but there is no direct
evidence that pinworms normally invade intestinal tissue
during their life cycle. Thus, it is not surprising that
invasive larvae were not detected deep within our patient’s
biopsy sections. We surmise that these developing
pinworms may provoke a eosinophilic mucosal
inflammatory reaction to parasite secretions or surface
antigens. Such a pathogenic mechanism may be similar to
that of eosinophilic enteritis due to A caninum7 or the
trichuris chronic dysentery syndrome.3 Enterobiasis is
extremely prevalent in human beings world wide, and
thus may account for some cases of unexplained
eosinophilic ileocolitis. In such patients, pinworm
412
infection should be sought by examination of the stool
and perianal skin for larvae, adult worms, or ova of
E vermicularis. Because asymptomatic enterobiasis is
common, further studies will be needed to address the
possible relation between E vermicularis and eosinophilic
ileocolitis.
We thank our colleagues who provided nematode material,
Dr David August for caring for the patient, Dr Larry Madoff for bringing
this case to our attention, and Dr Anil Rustgi, Dr Jamie Maguire, and
Dr Penny Noyce for review of the manuscript. This work was supported in
part by grants from the NIH and the Milton Fund of Harvard University
(LXL).
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Harvard-Thorndike Laboratory and Department of Medicine,
Division of Infectious Diseases (L X Liu MD, J Chi), and Department
of Pathology (M P Upton MD), Beth Israel Hospital and Harvard
Medical School, Boston, Massachusetts, USA; and Department of
Epidemiology, School of Public Health
(Prof L R Ash PhD), University of California, Los Angeles, California
Correspondence to: Dr Leo Liu, Division of Infectious Diseases,
Beth Israel Hospital, Dana 617, Boston, MA 02215, USA