Volume 119
Number 4
8. Hyman CL, Augenbraun MH, Roblin PM, Schachter J,
Hammerschlag M. Asymptomatic infection with Chlamydia
pneumoniae. Presented at the Oct. 21-24, 1990, meeting of the
Interscience Conference on Antimicrobial Agents and Che-
motherapy, Atlanta, Ga.
9. Grayston JT, Kuo CC, Wang SP, Altman J. A new Chlamy-
dia psittaci strain, TWAR, isolated in acute respiratory tract
infection. N Engl J Med 1986;315:161-8.
10. Li D, Daling JR, Wang SP, Grayston JT. Evidence that
Chlamydia pneumoniae, strain TWAR, is not sexually trans-
mitted. J Infect Dis 1989;160:328-31.
11. Porder K, Sanchez N, Roblin PM, McHugh M, Hammer-
Treatment of chronic cryptosporidial infection with
orally administered human serum immune globulin
Stephen M, Borowitz, MD, and Frank T, Saulsbury, MD
From the Department of Pediatrics, University of Virginia Health Sciences Center, Charlottes-
ville
Cryptosporidium is a protozoan capable of causing gastro-
enteritis in many animal species; it is a common cause of
gastroenteritis in children} In immunologically normal
children, the protozoan generally causes an acute, self-lim-
ited illness that is 5 to 10 days in duration and character-
ized by watery diarrhea, abdominal pain, and nausea}, 2 By
contrast, cryptosporidial infection in immunocompromised
children may produce severe, life-threatening diarrhea that
persists for months or years. 3-5 No uniformly effective ther-
apy for cryptosporidial infection has been identified. 6
We describe a child who experienced a prolonged
cryptosporidial infection while he was receiving mainte-
nance chemotherapy for acute leukemia. This patient, who
was treated with orally administered human serum immune
globulin, had prompt resolution of symptoms and disap-
pearance of the cryptosporidial infection.
CASE REPORT
Acute pre-B-cell leukemia was diagnosed in the patient, a
10-year-old boy. Remission was induced during the first month of
therapy with methotrexate, hydrocortisone, cytosine arabinoside,
g-asparaginase, and vincristine. For the next 6 months, the patient
received consolidation therapy, consisting of L-asparaginase and
high doses of methotrexate with leucovorin rescue. Thereafter,
Submitted for publication March 25, 1991 ; accepted May 10, 199 I.
Reprint requests: Stephen M. Borowitz, MD, Department of Pedi-
atrics, Box 386, University of Virginia Health Sciences Center,
Charlottesville, VA 22908.
9/22/30882
Clinical and laboratory observations 593
schlag M R. Lack of specificity of chlamydiazyme for detection
of vaginal chlamydial infection in prepubertal girls. Pediatr
Infect Dis J 1989;8:358-60.
12. Hammerschlag MR, Rettig P J, Shields ME. False positive re-
sults with the use of chlamydial antigen detection tests in the
evaluation of suspected sexual abuse in children. Pediatr Infect
Dis J 1988;7:11-4.
13. Dorian K J, Holtzhauer F, Myers WC, Moser JM, Halpin TJ.
False-positive results with the use of chlamydia tests in the
evaluation of suspected sexual abuse: Ohio, 1990. MMWR
1991;39:932-5.
maintenance therapy consisted of orally administered 6-mercap-
topurine at a dose of 75 rag/day and orally administered meth-
otrexate at a dose of 19 mg/wk.
While receiving maintenance chemotherapy, the patient had
persistent vomiting and diarrhea. Nausea and vomiting occurred
within I hour of meals; the diarrhea consisted of two or three large,
watery stools daily, without blood or mucus. The patient had mild,
crampy abdominal pain associated with bowel movements but no
tenesmus. Three weeks after the onset of symptoms, the child was
admitted to the University of Virginia Health Sciences Center.
Physical examination showed a thin child, chronically ill in
appearance. His weight was 31 kg, which was 9 kg less than a mea-
surement obtained 3 months previously. The remainder of the
physical examination was unremarkable.
Laboratory studies revealed a hemoglobin level of 14.4 gm/dl,
a platelet count of 417,000/~1, and a leukocyte count of 4000/~1,
with 79% neutrophils, 14% lymphocytes, and 3% eosinophils. The
serum sodium concentration was 128 mcq/L and the potassium
concentration was 3.3 meq/L. Serum chlorine, carbonic acid, glu-
cose, blood urea nitrogen, creatinine, alanine aminotransferase,
aspartate aminotransferase, and lactate dehydrogenase values were
normal. The total serum protein level was 3.7 gm/dl, with an al-
bumin level of 1.7 gm/dl. A bone marrow aspirate was normal. Se-
rum immunoglobulin concentrations were normal. The patient had
normal proportions of peripheral blood B cells, T cells, helper cells,
suppressor cells, and natural killer cells. Results of a polymerase
chain-reaction assay for human immunodeficiency virus comple-
mentary DNA and of a test for serum antibody to human immu-
nodeficiency virus were negative. Cultures of the feces for bacterial
pathogens and results of assays for Clostridium diffieile toxin and
rotavirus were negative. Examination of three separate stool spec-
imens failed to reveal any ova or parasites. Results of an upper
594 Clinical and laboratory observations
Figure. Intestinal biopsy specimen shows cryptosporidium oocysts (arrows) adherent to duodenal mucosa. (Hematoxy-
lin-eosin stain; original magnification X500,)
gastrointestinal tract x-ray series and an abdominal ultrasound ex-
amination were normal.
The patient continued to have diarrhea and vomiting, despite
therapy to treat the symptoms. He was unable to maintain hydra-
tion or adequate caloric intake by mouth. On the seventeenth hos-
pital day, he was taken to the operating room for the placement of
a central venous nutrition catheter. Esophagogastroduodenoscopy
at that time revealed distal esophagitis, a normal stomach with
widely patent pylorus, and diffuse erythema and friability of the
duodenum. Duodenal biopsy specimens demonstrated severe
cryptosporidial infection (Figure).
During the 5 days after operation, the patient continued to have
signs of an ileus and intermittent diarrhea. He was given 2.5 gm of
human serum immune globulin (Gamimune N; Miles-Cutter Lab-
oratories, West Haven, Conn.) through his nasogastric tube on 2
consecutive days. The ileus and diarrhea resolved promptly after
the second dose. The nasogastric tube was removed on the next day
and a clear liquid diet was started. During the next 3 days, the pa-
tient's feeding was advanced to a regular diet; he had no nausea,
abdominal pain, or diarrhea. Two weeks after the first examination,
results of a repeated esophagogastroduodenoseopy with duodenal
biopsy were entirely normal. The patient was discharged to his
home 2 days later. At discharge, the patient's serum electrolyte
values were normal, the total serum protein level was 6.7 gm/dl,
and the serum albumin concentration had increased to 3.1 gm/dl.
Within 3 months, the patient had gained 10 kg in body weight. The
patient has remained free of further gastrointestinal symptoms
during 6 months of follow-up observation.
DISCUSSION
The clinical course of cryptosporidial infection is influ-
enced to a large extent by the status of the patient's immune
system. Chronic cryptosporidial infection has been reported
The Journal of Pediatrics
October 1991
in children with congenital immunodeficiency diseases, 3, 4
in patients with acquired immunodeficiency syndrome, 6 and
in children who are receiving chemotherapy for cancer. 5
Our patient exhibited symptoms compatible with cryp-
tosporidial infection for 6 weeks before the diagnosis was
made. We found no evidence of other intestinal pathogens
that would account for the patient's symptoms.
There is currently no uniformly effective therapy for
cryptosporidial infection. Although some patients have had
encouraging responses to the macrolide antibiotic spiramy-
cin, most do not benefit from therapy with this agent. 6
Tzipori et al. 7 recently reported successful treatment of
chronic eryptosporidial infection in a child with congenital
immunodeficiency by means of oral administration of
hyperimmune bovine colostrum. The absence of effective
antibiotic therapy and the encouraging results reported by
Tzipori et al. 7 prompted us to administer human serum im-
mune globulin by mouth in an attempt to eradicate the
cryptosporidial infection in our patient. Several studies have
shown that commercially available human serum immune
globulin administered by mouth is effective in the preven-
tion and treatment &infectious gastroenteritis. 8, 9 Losonsky
et al. 8 demonstrated that human serum immune globulin
administered by mouth survived gastrointestinal passage in
an immunologically active form and was effective in erad-
icating chronic rotavirus infection in several children with
primary immunodeficiency diseases. Similarly, oral human
serum immune globulin has been reported to reduce the in-
cidence of infectious gastroenteritis among recipients of
bone marrow transplants. 9 Our patient's symptoms
promptly ceased after two oral doses of human serum im-
Volume 119
Number 4
mune globulin were given. Moreover, a repeated endoscopic
examination 14 days after oral immune globulin treatment
showed no evidence of residual cryptosporidial infection.
The details of the normal immune response to crypto-
sporidial infestation remain unclear. The occurrence of
chronic infection in patients with acquired immunodefi-
ciency syndrome suggests that cellular immunity is impor-
tant, but there is little definitive information in this regard.
Acute cryptosporidial infection is accompanied by the ap-
pearance of IgM and IgG serum antibody to the organism.1~
The important role of antibody in the normal immune re-
sponse is suggested by several reports of chronic crypto-
sporidial infection in children with congenital immunoglo-
bulin deficiency but intact cellular immunity.3, 4, 7 Seroep-
idemiologic studies indicate that 30% to 80% of healthy
adults have serum antibody to CryptosporidiumJ 1' 12 It is
thus likely that commercially available human serum
immune globulin preparations contain substantial quanti-
ties of IgG antibody to Cryptosporidium. This IgG may be
a valuable source of passive immunity in patients with
chronic cryptosporidial infection.
We conclude that a possible diagnosis of cryptosporidial
infection should be considered in any immunocompromised
child with chronic diarrhea. In addition, orally administered
human serum immune globulin appears to be effective
therapy for patients with chronic cryptosporidial infection.
REFERENCES
1. Soave R, Armstrong D. Cryptosporidium and eryptosporidi-
osis. Rev Infect Dis 1986;8:1012-23.
Acquired von Willebrand disease after Epstein-Barr
virus infection
Seiji Kinoshita, MD, Keiichiro Yoshioka, MD, Motoko Kasahara, and
Osamu Takamiya
From the Departments of Pediatrics and Clinical Laboratory, Osaka National Hospital, Osaka, Japan
Bleeding disorders with clinical and laboratory findings
similar to those of congenital von Willebrand disease,
known as acquired von Willebrand disease, may develop in
patients with autoimmune or lymphoproliferative diseases
Submitted for publication Jan. 24, 1991; accepted May 6, 1991.
Reprint requests: Seiji Kinoshita, MD, Department of Pediatrics,
Osaka National Hospital, 2-1-14, Hoenzaka, Chuo-ku, Osaka 540,
Japan.
9/22/30665
Clinical and laboratory observations 595
2. Wolfson JS, Richter JM, Waldron MA, Weber DJ, McCar-
thy DM, Hopkins CC. Cryptosporidiosisin immunocompetent
patients. N Engl J Med 1985;312:1278-82.
3. Lasser KH, Lewin KJ, Ryning FW. Cryptosporidial enteritis
in a patient with congenital hypogammaglobulinemia.Hum
Pathol 1979;10:234-40.
4. Sloper KS, Dourmashkin RR, Bird RB, Slavin G, Webster
ADB. Chronic malabsorption due to cryptosporidiosis in a
child with immunoglobulindeficiency.Gut 1982;23:80-2.
5. Miller RA, Holmberg RE, Clausen CR. Life-threatening di-
arrhea caused by cryptosporidium in a child undergoing ther-
apy for acute lymphocytic leukemia. J PEDIATR 1983;
103:256-9.
6. Centers for Disease Control. Treatment of eryptosporidiosisin
patients with acquired immunodeficiencysyndrome (AIDS).
MMWR 1984;33:117-9.
7. Tzipori S, Robertson D, Chapman C. Remission of diarrhoea
due to cryptosporidiosis in an immunodefieientchild treated
with hyperimmune bovine colostrum. BMJ 1986;293:t276-7.
8. LosonskyGA, Johnson JP, Winkelstein JA, Yolken RH. Oral
administration of human serum immunoglobulinin immuno-
deficient patients with viral gastroenteritis. J Clin Invest
1985;76:2362-7.
9. Tutschka PJ. The use of immunoglobulin in bone marrow
transplantation. J Clin lmmunol 1990;10(Suppl):88-92.
10. Ungar BLP, Soave R, Fayer R, Nash TE. Enzyme immunoas-
say detection of immunoglobulin M and G antibodies to
Cryplosporidium in immunocompetent and immunocompro-
raised persons. J Infect Dis 1986;153:570-7.
11. Tzipori S, Campbell I. Prevalence of cryptosporidium anti-
bodies in 10 animal species. J C[in Microbiol 198t;14:455-6.
12. Ungar BPL, Mulligan M, Nutman TB. Serologic evidenceof
cryptosporidium infection in US volunteers before and during
Peace Corps service in Africa. Arch Intern Med 1989;149:
894-7.
or malignant tumorsJ 6 We describe a case of acquired
von Willebrand disease after Epstein-Barr virus infection.
CASE REPORT
A 6-year-old girl with no family history of bleeding disorder and
no previous symptoms of bleeding had peteehiae on the chest and
bruises on the lower legs 2 weeks after a febrile illness associated
with a milialial reddish eruption. Investigations of hemostasis
showed a prolonged bleeding time (>30 minutes) with normal
platelet count (354 • 103/~zl),decreased platelet retention (16% by
the Salzmann method), decreased factor VIII coagulant activity