Download Isolated Splenic Cat Scratch Disease in an

BRIEF REPORT
Isolated Splenic Cat Scratch
Disease in an Immunocompetent
Adult Woman
Jacob Gilad,1,2,4 Arik Wolak,1,4 Abraham Borer,1,2,4 Daniel Benharroch,3,4
Boaz Avidor,5 Michael Giladi,5 and Francisc Schlaeffer1,2,4
Department of Internal Medicine E, 2Infectious Disease Institute,
and 3Pathology Institute, Soroka University Medical Center, and 4Faculty
for Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva,
and 5Bernard Pridan Laboratory for Molecular Biology of Infectious Diseases,
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
1
We report a case of isolated splenic cat scratch disease in an
immunocompetent woman. The clinical presentation of prolonged fever, night sweats, weakness, and intrasplenic lesions
was highly suggestive of lymphoma. This is the second reported case of isolated splenic cat scratch disease in an adult
and the first in a healthy adult.
Cat scratch disease (CSD) caused by Bartonella henselae frequently causes fever and lymphadenopathy in immunocompetent patients, especially children [1]. CSD seldom affects
other organ systems, such as the liver or spleen. Isolated splenic
CSD is extremely rare, and only a few cases have been reported
to date.
We report a case of isolated splenitis due to active B. henselae
infection in an immunocompetent woman who presented with
fever of unknown origin. To our knowledge, isolated splenic
CSD in an immunocompetent adult has not previously been
reported.
Materials and methods. EIA was done using N-lauroylsarcosine–insoluble outer membrane antigens from B. henselae
to detect anti–B. henselae IgM and IgG in samples of the patient’s blood, as described elsewhere [2]. Octane was used to
extract DNA from paraffin-embedded specimens. DNA was
amplified from a 281-bp fragment of the 16S rRNA gene of B.
henselae, using Bartonella-specific primers (p12B and p24E) [3].
The PCR products were transferred to a nylon membrane and
hybridized, under stringent conditions, with a B. henselae–
Received 14 December 2001; accepted 5 August 2002; electronically published 10 December
2002.
Reprints or correspondence: Dr. Jacob Gilad, Infectious Disease Institute, Soroka University
Medical Ctr., PO Box 151, Beer-Sheva, 84101 Israel ([email protected]).
Clinical Infectious Diseases 2003; 36:e10–3
2003 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2003/3601-00E4$15.00
e10 • CID 2003:36 (1 January) • BRIEF REPORT
specific probe [4] by means of the digoxigenin labeling system,
as described elsewhere [5].
Positive controls included pus aspirated from a lymph node
in another patient with CSD and B. henselae isolate BhTA-2
(from a patient with CSD described elsewhere [5]). Negative
controls included DNA extracted from a paraffin-embedded
specimen of a lymph node with metastatic carcinoma, pus from
non-CSD bacterial lymphadenitis, PCR reagents without DNA,
and water.
Case report. A 43-year-old otherwise healthy white woman
was admitted to the hospital because of fever of unknown
origin. One month earlier, during an outpatient visit to a physician, she had begun complaining of fever (temperature,
39.0C) accompanied by generalized weakness and night sweats.
Temporary defervescence was noted after empirical treatment
with amoxicillin and later with cefuroxime-axetil, but the symptoms recurred shortly thereafter. She had no underlying diseases
and was not taking medications or using alcohol or illicit drugs.
There was no history of recent travel. She reported raising “a
healthy dog and a few parrots” but denied having been bitten.
On examination, the patient appeared to be well. Her oral
temperature was 36.8C, and her heart rate was 117 beats/min.
Other findings of the physical examination were unremarkable.
Of note, lymph nodes, liver, and spleen were not enlarged.
The following values were measured in samples of the patient’s blood: WBC count, 9500 cells/mm3 (normal differential);
hematocrit, 32%; hemoglobin level, 10.3 g/dL (normal indices);
platelet count, 236,000 platelets/mm3; and erythrocyte sedimentation rate, 65 mm/h. The results of a chemistry panel,
including liver function tests, were within normal limits; the
results of electrocardiographic and chest radiographic examination and of urinalysis all were normal. The results of serologic
testing were negative for Epstein-Barr virus; cytomegalovirus;
hepatitis viruses A, B, and C; adenovirus; Chlamydia, Toxoplasma, Rickettsia, and Brucella species; HIV; rheumatoid factor;
and anti-nuclear antibodies.
Complement, immunoglobulin subclass, and fibrinogen levels were normal. The C-reactive protein level was 5.9 mg/dL
(normal range, 0–0.8 mg/dL). Cultures of 5 sets of blood samples and of urine yielded negative results (sterile). A tuberculin
skin test was nonreactive, and no acid-fast bacilli were found
in sputum. The results of thyroid function tests and protein
electrophoresis were normal. The fever persisted. Repeated
questioning revealed that the patient was raising numerous cats
and kittens for business purposes.
A CT scan of the abdomen demonstrated multiple hypodense
areas within the splenic parenchyma, with minimal splenomegaly (figure 1). The liver appeared normal. Echocardiography yielded normal results. Testing of a bone marrow biopsy
specimen revealed a slightly to moderately hypercellular marrow, with normal maturation and no evidence of malignancy.
A diagnostic splenectomy was done. Macroscopic examination revealed a slightly enlarged multinodular spleen. Microscopic examination revealed necrotizing granulomata with
peripheral palisaded epithelioid cells, plasma cells, and rare
multinucleated Langhans-type giant cells involving the red
pulp. Foci of necrosis with numerous granulocytes, stellate abscesses, and occasional nonnecrotizing granulomata were evident (figure 2). The white pulp showed follicular hyperplasia.
Stains for acid-fast bacilli and fungi yielded negative results.
The pathologist considered these findings to be suggestive of
CSD. A Warthin-Starry silver stain was not made.
Results of EIA were positive for anti–B. henselae IgM and
negative for IgG in the acute-phase serum sample obtained on
the first week of illness. Convalescent-phase serum samples
obtained on weeks 8 and 11 were negative for anti–B. henselae
IgM but positive for IgG. Paraffin-embedded spleen tissue was
subjected to PCR and hybridization, which identified B. henselae DNA. Marked clinical improvement and near-immediate
defervescence was noted shortly after surgery. The patient was
subsequently discharged without additional therapy and was
doing well 11 year after the splenectomy.
Discussion. B. henselae is a small gram-negative bacillus
that can produce 2 entirely different pathologic reactions, depending on the immune status of the host: CSD, which is
characterized by granulomatous nonangiogenic inflammation,
and angiogenesis, in which a neutrophilic inflammatory response to bacilli located within the skin, bone, and other organs
(bacillary angiomatosis) or the liver and spleen (peliosis) is
seen. CSD mainly occurs in immunocompetent hosts, whereas
bacillary angiomatosis mainly affects immunocompromised
persons, especially those with HIV infection [6].
CSD, which was first described in 1950 [7], typically begins
with a localized papule that appears 3–5 days after a cat scratch
and progresses into a pustule. Tender regional lymphadenopathy typically develops within 1–2 weeks after inoculation [1,
8–10]. Systemic symptoms are frequent; they include fever, malaise, anorexia, and weight loss and may persist if the individual
does not receive therapy [9, 10]. The majority of cases have
occurred in patients !20 years of age [9], although recent data
suggest that CSD may be more common among adults than
previously has been recognized [10]. CSD may cause a myriad
of clinical presentations and thus may masquerade as other
syndromes and may be difficult to diagnose. Atypical CSD may
occur in up to 11% of cases, and almost any organ may be
involved [8].
We present here a case of isolated splenic CSD caused by B.
henselae. The history of close contact with cats and kittens, the
radiologic and histopathologic findings, the IgG and IgM seroconversion (as determined by EIA), and the identification of
Figure 1. Axial CT scan at level of kidneys without contrast media. Multiple hypodense lesions are evident within the splenic parenchyma. The
spleen is only slightly enlarged.
BRIEF REPORT • CID 2003:36 (1 January) • e11
Figure 2. Pathologic examination of the spleen. Macroscopic examination (top) reveals a slightly enlarged, multinodular spleen. Microscopic
examination (bottom) shows a pathologic process involving the red pulp, with necrotizing granulomata and foci of necrosis with numerous granulocytes,
stellate abscesses, and occasional nonnecrotizing granulomata. Follicular hyperplasia is present in the white pulp. (Hematoxylin-eosin stain; original
magnification, ⫻240.)
B. henselae DNA using PCR and hybridization all favor this
diagnosis. The EIA used in this report was recently evaluated
in a large study of 84 patients with PCR-confirmed CSD. The
specificity of this assay was found to be as high as 98%–100%
and 99%–100% for IgG and IgM, respectively, as determined
by testing of 3 control groups that included healthy subjects,
patients suspected clinically of having CSD but eventually found
to have other definite diagnoses, and patients with non-CSD
acute infections with IgM response [2].
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This case also demonstrates the importance of the IgM assay.
The availability of an EIA for anti–B. henselae IgM is one advantage to use of the EIA, compared with the immunofluorescent antibody test; the latter was developed primarily for
the detection of anti–B. henselae IgG and has not been routinely
applied for the detection of IgM antibodies. The EIA, like the
immunofluorescent antibody test, may not distinguish between
the various species of Bartonella because of serologic crossreactivity and, therefore, cannot by itself confirm the diagnosis
of B. henselae infection. The primers used for the PCR assay
are specific for the Bartonella genus and may, therefore, amplify
pathogenic Bartonella species other than B. henselae. However,
the oligonucleotide probe used for hybridization is species specific (based on screening of GenBank using BLAST software)
and is expected to recognize B. henselae DNA sequence and
not other pathogenic Bartonella species, such as Bartonella quintana, Bartonella clarridgeiae, and Bartonella elizabethae.
In 2 series that included 28 children with hepatosplenic CSD,
5 had splenic involvement without hepatic involvement, but
lymphadenopathy was uniformly present [11, 12]. In yet another series, which included 11 children with hepatosplenic
CSD, 5 had no lymphadenopathy and 3 had splenic involvement without hepatic involvement [13]. Among 42 cases of
hepatosplenic B. henselae infection (22 in children and 20 in
adults), both the liver and the spleen were affected in 22 cases;
the liver only, in 16 cases; and the spleen only, in 4 [6]. Two
cases involving only the spleen occurred in healthy children
and 2 occurred in adults. One of these adults had cancer and
splenic bacillary peliosis, and the other had hereditary spherocytosis and diabetes mellitus accompanied by splenomegaly and
a solitary splenic lesion caused by CSD [14]. A search of the
literature did not reveal additional cases of isolated splenic CSD
in adults. The case described here, therefore, is the second case
to be reported of isolated splenic CSD in an adult and the first
in a healthy patient.
In conclusion, this case represents an unusual manifestation
of atypical CSD in an immunocompetent adult. When B symptoms (weight loss, low-grade prolonged fever or fever of unknown origin, and night sweats) and splenic involvement are
present, as in the case under discussion, systemic CSD may
easily be confused with lymphoproliferative malignancy [9, 15],
and this confusion may result in performance of invasive diagnostic procedures, such as laparotomy. A complete medical
history should be taken and a high index of suspicion maintained for diagnosis of atypical CSD in adults. Serologic testing
and molecular methods such as PCR may be necessary aids in
establishing the diagnosis.
References
1. Bass JW, Vincent JM, Person DA. The expanding spectrum of Bartonella
infections. II. Cat-scratch disease. Pediatr Infect Dis J 1997; 16:163–79.
2. Giladi M, Kletter Y, Avidor B, et al. Enzyme immunoassay for the
diagnosis of cat-scratch disease defined by polymerase chain reaction.
Clin Infect Dis 2001; 33:1852–8.
3. Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins LS. The agent
of bacillary angiomatosis: an approach to the identification of uncultured pathogens. N Engl J Med 1990; 323:1573–80.
4. Alkan S, Morgan MB, Sandin RL, Moscinski LC, Ross CW. Dual role
of Afipia felis and Rochalimaea henselae in cat scratch disease. Lancet
1995; 345:385.
5. Avidor B, Kletter Y, Abulafia S, Golan Y, Ephros M, Giladi M. Molecular
diagnosis of cat scratch disease: a two-step approach. J Clin Microbiol
1997; 35:1924–30.
6. Liston TE, Koehler JE. Granulomatous hepatitis and necrotizing splenitis due Bartonella henselae in a patient with cancer: case report and
review of hepatosplenic manifestations of Bartonella infection. Clin
Infect Dis 1996; 22:951–7.
7. Debre R, Lamy M, Jammet M, et al. La maladie des griffes de chat.
Bull Mem Soc Med Hop Paris 1950; 66:76–9.
8. Schwartzman WA. Infections due to Rochalimaea: the expanding clinical spectrum. Clin Infect Dis 1992; 15:893–902.
9. Carithers HA. Cat-scratch disease: an overview based on a study of
1,200 patients. Am J Dis Child 1985; 139:1124–33.
10. Zangwill KM, Hamilton DH, Perkins BA, et al. Cat scratch disease in
Connecticut: epidemiology, risk factors, and evaluation of a new diagnostic test. N Engl J Med 1993; 329:8–13.
11. Sami Arisoy E, Correa AG, Wagner ML, Kaplan SL. Hepatosplenic catscratch in children: selected clinical features and treatment. Clin Infect
Dis 1999; 28:778–84.
12. Ventura A, Massei F, Not T, Massimetti M, Bussani R, Maggiore G.
Systemic Bartonella henselae infection with hepatosplenic involvement.
J Pediatr Gastroenterol Nutr 1999; 29:52–6.
13. Dunn MW, Berkowitz FE, Miller JJ, Snitzer JA. Hepatosplenic catscratch disease and abdominal pain. Pediatr Infect Dis J 1997; 16:
269–72.
14. Tappero JW, Keohler JE, Berger TG, et al. Bacillary angiomatosis and
bacillary splenitis in immunocompetent adults. Ann Intern Med
1993; 118:363–5.
15. Wong TZ, Kruskal J, Kane RA, Trey G. Cat-scratch disease simulating
lymphoma. J Comput Assist Tomogr 1996; 20:165–6.
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