Adult systemic cat scratch disease associated with therapy for hepatitis C

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Adult systemic cat scratch disease associated with therapy for hepatitis C

Zahida Bhatti and S Berenson

Infectious Disease Division, VA Western New York Healthcare System, State

University of New York at Buffalo School of Medicine, Buffalo, New York

14215, USA

BMC Infectious Diseases 2007, 7:8 doi:10.1186/1471-2334-7-8

The electronic version of this article is the complete one and can be found

online at: http://www.biomedcentral.com/1471-2334/7/8

Received 18 September 2006

Accepted 23 February 2007

Published 23 February 2007

© 2007 Bhatti and Berenson; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative

Commons Attribution License (http://creativecommons.org/licenses/by/2.0),

which permits unrestricted use, distribution, and reproduction in any

medium, provided the original work is properly cited.

Abstract

Background

We describe the first case of systemic cat scratch disease in a patient

receiving peginterferon & #945;-2a and ribavirin for treatment of hepatitis

C. Cases of adult systemic CSD are extremely infrequent and immunomodulatory

treatment for hepatitis C has been associated with aberrant host responses

to common pathogens.

Case presentation

A 52 year old man being treated for hepatitis C presented with diffuse

lymphadenopathy, weight loss, fevers and splenic lesions. Symptoms were

initially confused with adverse effects of his regimen, delaying recognition

of his infection. Diagnostic investigation, including histopathology,

microbiology and serologic parameters, confirmed that his illness was due to

disseminated cat scratch disease with Bartonella henselae.

Conclusion

Disseminated CSD is exceptionally rare in adults. We describe the first case

of disseminated cat scratch disease associated with peginterferon & #945; and

ribavirin to alert clinicians of the need to be aware of unusual

manifestations of common infections in this population.

Background

Cat scratch disease (CSD) most commonly presents as a localized

granulomatous and suppurative lymphadenopathy caused by Bartonella henselae,

a small fastidious gram-negative argyrophillic bacillus [1,2]. While the

overwhelming majority of systemic CSD occurs in children, especially with

hepatosplenic involvement, disseminated CSD is exceedingly rare in

immunocompetent adults [3,4].

Interferon & #945; and ribavirin are mainstays of treatment for chronic

hepatitis C, that have been associated with aberrant immune-mediated host

responses, that may resemble adverse pharmacologic effects. In this report,

we present the first description of disseminated CSD in an adult receiving

interferon 2a and ribavirin for treatment of chronic hepatitis C, in whom

signs and symptoms were initially confused with adverse effects of

medications. We offer our experience to alert clinicians of the need for

awareness of unusual manifestations of commons infections in this

population.

Case Presentation

A 52-year-old male with a history of hepatitis C, genotype 1b, was nearing

completion of a one-year course of treatment with pegylated interferon 2a

(180 ug subcutaneously each week) and ribavirin (1200 mg orally each day).

His initial hepatitis C viral RNA had declined from 2.2 × 106 IU/ml at onset

of treatment, to <65 IU/ml by six months, and remained undetectable

thereafter. Toward the end of his course of treatment, he developed fatigue,

malaise, drenching night sweats, intermittent fever and chills. On the last

visit for hepatitis C treatment, axillary and cervical lymphadenopathy was

noticed. His symptoms were initially attributed to adverse effects of

interferon & #945;, prompting premature discontinuation of treatment after

10.5 months. One month after onset of symptoms, he presented to a nearby

hospital for further workup.

He was transferred to the Buffalo VA Western New York Healthcare System with

complaints of malaise and left sided mid back pain. He had a documented

weight loss of 40 lbs over the previous year. He appeared chronically ill

and fatigued. He had a temperature of 101°F and a heart rate of 105 beats

per minute. Generalized lymphadenopathy was noted, including cervical,

axillary, inguinal and right epitrochlear lymph nodes. The nodes were 1–2 cm

wide, firm, movable and nontender. He had left sided abdominal fullness and

mild tenderness, but no guarding or rebound. The remainder of his

examination was noncontributory.

CBC revealed hemoglobin of 11.7 g/dl (13.5–17), white blood cell count of

7.6 K/cmm (4.4–10.7), platelet count of 511 K/cmm (140–375) and ESR of 80

mm/hr. Serum chemistries included a sodium of 130 mEq/L (135–145),

creatinine of 0.9 mg/dl (0.7–1.4). SGOT was 68 units/l (12–34), SGPT: 95

units/l (25–65). A serum ELISA for human immunodeficiency virus was

negative. Rheumatoid and anti-nuclear antibody titers were also negative.

Computerized tomography (CT) scan of chest and abdomen revealed mild

lymphadenopathy and multiple contrast enhancing hypodense lesions in the

spleen (Figure 1).

Initial clinical suspicion included lymphoma and he underwent a lymph node

biopsy. Further history revealed exposure to numerous cats. He frequented a

neighbor who had 6–9 cats, including kittens, with which the patient had

played, and from whom he received numerous scratches. Serologic studies were

sent for antibodies to Bartonella, Chlamydia, Toxoplasma and Brucella. He

was given ibuprofen for symptomatic relief.

A biopsy of an epitrochlear lymph node displayed necrotizing granulomata

with peripheral palisading epithelioid cells, with an admixture of plasma

cells and lymphocytes. Areas of stellate necrosis with microabscesses were

evident, consistent with cat scratch disease (Figure 2). Stains for

acid-fast bacilli and fungi showed no organisms. Lymph node biopsy material

was cultured for routine pathogens, acid-fast bacilli and fungal organisms.

Although the Gram stain displayed abundant white blood cells, all cultures

were sterile.

Over the next 3–4 days, the patient defervesced and improved symptomatically

on ibuprofen alone. By the eighth day, serum antibody titers (IgG and IgM)

for Bartonella henselae were reported as >1:16,384. He continued to improve

without further treatment. Six months later he was doing well and had

regained 25 lbs of weight. An abdominal CT scan revealed complete resolution

of splenic lesions.

Conclusion

This is the first reported case of systemic CSD with generalized

lymphadenopathy and splenic involvement in an adult associated with

immunomodulatory treatment for hepatitis C. In our patient, the diagnosis of

CSD was established by: 1) history of exposure to cats, 2) obtaining sterile

pus from a lymph node with no growth on routine cultures, 3) lymph node

biopsy displaying classic findings of necrotizing stellate granulomata with

microabscesses, and 4) an extremely high titer serum antibody response to B.

henselae.

Cat scratch disease was first described in 1950 [5], although manifestations

that constitute the disease have been known for over 100 years. Typically

lesions may appear at the site of a cat scratch, often from a young kitten,

as a papule, pustule or vesicle, followed by fever, regional lymphadenopathy

and occasional systemic symptoms. Illness is usually self-limited, resolving

in 2–3 months with no treatment. Atypical signs and symptoms occur most

often in children and include Parinaud's oculoglandular syndrome

(conjunctivitis, conjunctival granulomata with preauricular

lymphadenopathy), encephalitis, myelitis, hepatosplenic disease and

dissemination [6,7]. Rarely, splenic CSD may require splenectomy [8,9]. The

clinical resemblance to lymphoma, of splenic abscesses in disseminated CSD

such as our patient presented with, has been described [10].

Laboratory diagnosis of CSD includes appropriate histological findings and

detection of serum antibodies to B. henselae by enzyme immunoassay, which

has a specificity of up to 95% and sensitivity of 83–95%, when IgM titer is

greater than 1:250 [11,12]. PCR assay of tissue or blood, although not

employed routinely, may have high sensitivity and specificity [13]. PCR

techniques have been applied to immunofluorescent detection of B. henselae

in tissue sections. Although sensitivity of this method has been variable,

high specificity of positive samples may be of value when the diagnosis is

in question [14,15]. Recent reports of high sensitivity of

immunohistochemistry with monoclonal antibodies to B. henselae, tested on a

limited numbers of tissue samples, suggest potential future value [16].

Although well characterized, these techniques are not universally employed

[17].

While the specific factors that permit dissemination of CSD are not known,

clinical experience confirms that the host response to B. henselae

contributes to the manifestation of disease. This is illustrated by the

experience with B. henselae in AIDS patients, where the same pathogen that

causes self-limited regional lymphadenopathy in immunocompetent hosts,

causes bacillary angiomatosis and peliosis hepatis [18]. However, other

immunodeficient states, such as chronic lymphocytic leukemia and T cell

lymphoma, can also trigger dissemination of CSD [19,20]. In fact, the

immunomodulatory effects of co-infection with EBV may have been responsible

for one case of disseminated CSD [21].

Although the impact of interferon & #945; and ribavirin on host immune

response has had limited characterization, aberrant host responses

associated with this regimen are well known, including immune-mediated

Graves' disease and sarcoidosis [22]. Although advanced forms of infection,

including visceral leishmaniasis [23] have been reported with

interferon- & #945; and ribavirin therapy, a major focus of infectious

complications has been associated with drug induced neutropenia [24]. This

was clearly not the case in our patient. Interferon & #945; exerts biological

activities by binding to cell membranes receptors, initiating numerous

cellular events, including upregulation of Th1 cells and modulation of

immunological activities of macrophages and lymphocytes [25]. While the

precise clinical relevance of these events is not known, it is difficult to

ignore the temporal relationship between administration of this regimen and

onset of disease in our patient, most likely due to immunomodulatory

factors, aside from neutropenia, affected by this regimen. In addition,

adverse effects of therapy, including flu-like symptoms, fatigue (47–64%),

fever (39–46%), and rigors (35%), were also present at the onset of our

patient's illness, resulting in delayed recognition of his infection [26].

The success and increasing utilization of interferon & #945; and ribavirin

for treatment of hepatitis C will undoubtedly reveal a greater number of

interferon-related side effects in the future. We offer the experience of

our patient to alert clinicians of the need to be aware of aberrant

presentations of infections in this population.

Competing interests

The author(s) declare that they have no competing interests.

Authors' contributions

Both authors (ZB and CSB) contributed equally to the research and design of

this manuscript.

Acknowledgements

The authors are grateful to F. , M.D., for critical reading of

this manuscript. Written consent was obtained from the patient's relative

for publication of this case report. This study was accomplished with

support from the Department of Veteran's Affairs.

References<snip>

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