Disseminated Bartonella henselae
Brief history of the Present Illness: For example, “A 25-year-old male presented with…”
A 59-year-old male with a history of idiopathic dilated cardiomyopathy who underwent orthotopic heart transplantation 12 years prior to presentation, atrial fibrillation, and chronic kidney disease stage 3 presented to the hospital with fever, night sweats, and fatigue.
One week prior to admission, he saw his primary care doctor for evaluation of a superficial right thigh nodule and right inguinal lymphadenopathy. He was started on trimethoprim-sulfamethoxazole for a presumed soft tissue infection. He subsequently noted fevers of 38 degrees Celsius. When these fevers persisted despite antibiotics, he presented to the emergency department and was admitted to the hospital. Blood cultures were obtained, and the patient was initiated on empiric intravenous vancomycin and piperacillin-tazobactam.
Past Medical History including allergies (if relevant):
He has a history of non-ischemic cardiomyopathy, orthotopic heart transplantation (cytomegalovirus donor +/recipient -) 12 years prior to presentation, atrial fibrillation, dyslipidemia, and chronic kidney disease stage 3 (baseline creatinine 1.6 mg/dl).
Key Medications (if relevant):
Medications included aspirin 81mg daily, tacrolimus 1mg/0.5 milligrams daily, mycophenolate 1500 milligrams twice daily, diltiazem 360 milligrams daily, ezetimibe 5 milligrams daily, and rosuvastatin 5 milligrams daily.
Epidemiological history (if relevant, such as habits, social and family history, animal exposures or travel):
The patient lives in suburban Virginia with his wife and works as a nuclear engineer in an office setting. He has never smoked or used illicit drugs. He rarely drinks alcohol. He is a competitive tennis player. He has never traveled out of the country. The patient denies history of homelessness or incarceration. He has no known exposure to tuberculosis. He has not had recent sick contacts. He and his wife feed outdoor cats, but he does not have any direct contact with the cats. The patient does not have other exposure to animals.
Physical Examination: General description, vital signs, and other relevant physical findings. For example, “The patient appeared well. The blood pressure was 120/80 mm Hg, pulse 72 beats per minute, temperature 98.6oF (37.0oC), and respirations 20 breaths per minute. The examination was otherwise normal.” Please refer to appropriate figures of physical findings if provided (Figure 1, Figure 2, etc.). Please avoid the use of abbreviations.
The patient appeared well. He was walking multiple laps around the hospital floor without difficulty. Temperature was 38 degrees Celsius, blood pressure 103/66, pulse 90, respiratory rate 17, pulse oximetry 98% on room air. Cardiac exam notable for a II/VI systolic murmur at the right upper sternal border. Skin exam was notable for a 1 centimeter right medial thigh nodule with induration but no surrounding fluctuance or erythema. There was no drainage, and the nodule was not tender to palpation. He had an enlarged, nontender right inguinal lymph node. The remainder of the exam was normal.
Studies: Relevant laboratory findings (with units of measurement and normal reference ranges as these vary among institutions), radiology, etc. For example, “The hematocrit was 35.0% (reference range 41.0-53.0 in men), and the other routine laboratory test results were normal. A chest radiograph revealed a pulmonary nodule (1 cm in diameter) in the right upper lung field).” Please include pertinent positives and negatives. Refer to figures if appropriate.
At admission, the white blood cell count was 4.7 (reference 3.2-9.8): 58% neutrophils (reference 37-80%), 25% lymphocytes (reference 10-50%), 14% monocytes (reference 0-1%). Hemoglobin 16.4 (reference 13.7-17.3), platelets 202 (reference 150-450). Creatinine was 1.9 (reference 0.6-1.3). Aspartate transaminase was 55 (reference 15-41), alanine transaminase was 60 (reference 17-63), alkaline phosphatase was 87 (reference 24-110), total bilirubin was 0.7 (reference 0.4-1.5).
Two sets of blood cultures from admission showed no growth after five days. Urinalysis demonstrated no evidence of infection. Chest radiograph demonstrated no cardiopulmonary abnormality. Transthoracic echocardiogram noted mild left ventricular hypertrophy without evidence of vegetation or valvular dysfunction. Ejection fraction was 55% with normal diastolic function.
Bedside incision and drainage of the right thigh nodule had a negative Gram stain, bacterial, and fungal culture.
Clinical Course Prior to Diagnosis (if relevant): Note Figures if appropriate.
He continued to have fevers as high as 39.4 degrees Celsius and developed progressive fatigue and night sweats.
Liver function tests continued to increase during admission: aspartate transaminase increased from 55 to 86, alanine transaminase from 60 to 127, total bilirubin from 0.7 to 1.0, and alkaline phosphatase from 87 to 165. Serum human immunodeficiency virus, cytomegalovirus, and epstein-barr virus quantitative polymerase chain reactions were negative. Right upper quadrant ultrasound demonstrated no gallstones or evidence of cholecystitis. A 1.4 cm hyperechoic lesion was seen in the posterior aspect of the left liver lobe consistent with a hemangioma.
His thigh nodule remained stable in size without drainage. The nodule and his inguinal lymph node were biopsied.
Review of a peripheral blood smear demonstrated multiple atypical lymphocytes, raising concern for hematologic malignancy. Positron emission tomography scan was performed. This demonstrated hypermetabolic retroperitoneal, pelvic, left adrenal, and right inguinal lymphadenopathy along with diffuse splenic uptake.
- Bartonella henselae
- Posttransplant lymphoproliferative disease
Diagnostic Procedure(s) and Result(s):
Bartonella serologies (IgG and IgM) were negative (reference ranges <1:320 and <1:100 titers, respectively) and serum toxoplasma PCR was negative. Serum cryptococcal antigen and urine histoplasma antigen were also negative.
Skin biopsy of the thigh lesion revealed dense acute and chronic inflammation. Special stains did not reveal an infectious etiology.
Inguinal lymph node biopsy revealed suppurative granulomatous lymphadenitis and no evidence of malignancy. Warthin-Starry stain showed rod-shaped organisms. Serum qualitative Bartonella henselae PCR was positive. Bartonella henselae PCR of the inguinal lymph node tissue subsequently returned positive.
The patient was started initially on oral azithromycin 500 milligrams for three days, which was then decreased to 250 milligrams daily, and oral doxycycline 100 milligrams twice daily. Fevers rapidly improved, and he was discharged within the next 48 hours. He was seen in clinic 3 weeks and 3 months after discharge. He continued to clinically improve, and by the three month follow-up appointment, he reported he was back at his baseline energy level. His antibiotics were stopped at that appointment.
Brief Discussion of Differential/Major Teaching points of case:
The Bartonella species are gram-negative bacilli, of which Bartonella henselae and Bartonella quintana are the most common in North America. Human infection is typically associated with cat and flea exposure, particularly young cats.  Individuals with intact immune systems typically present with a localized and self-limited lymphadenitis near the site of inoculum, referred to as cat scratch disease. Bartonella has also been identified as an etiology of culture-negative endocarditis, especially in adult patients with prior valvular disease. However, individuals who are immunosuppressed, particularly patients with HIV/AIDS and organ transplant recipients, are at increased risk of disseminated infection. Infection in the HIV/AIDS population typically presents with vasoproliferative lesions. Bacillary angiomatosis most commonly manifests as cutaneous lesions, while bacillary peliosis presents as vascular lesions of the liver and spleen. In contrast, transplant patients present more frequently with granulomatous and suppurative lesions. There is not a clear correlation between type or duration of immunosuppression and the development of vascular versus granulomatous infection.
In the solid organ transplantation population, there is an increased frequency of cases of bartonellosis reported in renal transplant patients, followed by liver, then lung and heart transplant recipients, likely due to the proportion of each of these transplants performed annually. Time from transplantation to infection has been reported anywhere from 1 month to 14 years. Patients often present with disseminated infection earlier in their post-transplant course, while those with localized cat scratch disease typically present later (likely due to decreases in immunosuppression over time). Most cases are transmitted by feline exposure, although there have been reported cases of transmission of infection from the transplanted organ. Immunosuppression can also reactivate prior infection.
Solid organ transplant recipients with disseminated bartonellosis often present with nonspecific symptoms such as fever, night sweats, and headache, though some have clinical evidence on exam of hepatomegaly and splenomegaly. Diagnosis can be made by serology, polymerase chain reaction, culture, and histopathology. Serology is usually positive but can be negative early in the disease course. Pathology often shows granulomas, and the Warthin-Starry silver stain highlights the Bartonella bacilli.
Treatment patterns vary based on the degree of dissemination of the infection. Localized cat-scratch disease in an immunocompetent host often does not require treatment, as it is self-limited. If antibiotics are prescribed, the first-line agent is usually azithromycin, which can expedite improvement in lymphadenopathy. No specific guidelines exist for immunocompromised hosts with disseminated bartonellosis. Clinical practice is guided by case reports and expert opinion. Macrolides are often used as monotherapy or in combination with doxycycline.[7, 11, 12] Patients may also benefit from a reduction in immunosuppression. Duration of therapy ranges from a few weeks to several months, depending on the degree of dissemination and clinical response.
Disseminated Bartonella henselae
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- Spach, D.H. and J.E. Koehler, Bartonella-associated infections. Infect Dis Clin North Am, 1998. 12(1): p. 137-55. PMID: 9494835
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- Antar, A.A.R., et al., Disseminated cat-scratch disease presenting as nausea, diarrhea, and weight loss without fever in a heart transplant recipient. Transpl Infect Dis, 2017. 19(3). PMID: 28199763
- Gasquet, S., et al., Bacillary angiomatosis in immunocompromised patients. Aids, 1998. 12(14): p. 1793-803. PMID: 9792380
- Rostad, C.A., et al., Bartonella henselae-mediated disease in solid organ transplant recipients: two pediatric cases and a literature review. Transpl Infect Dis, 2012. 14(5): p. E71-81. PMID: 22862881
- Psarros, G., et al., Bartonella henselae infections in solid organ transplant recipients: report of 5 cases and review of the literature. Medicine (Baltimore), 2012. 91(2): p. 111-21. PMID: 22391473
- Scolfaro, C., et al., Possible donor-recipient bartonellosis transmission in a pediatric liver transplant. Transpl Infect Dis, 2008. 10(6): p. 431-3. PMID: 18651873
- Agan, B.K. and M.J. Dolan, Laboratory diagnosis of Bartonella infections. Clin Lab Med, 2002. 22(4): p. 937-62. PMID: 12489289
- Bass, J.W., et al., Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J, 1998. 17(6): p. 447-52. PMID: 9655532
- Rolain, J.M., et al., Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother, 2004. 48(6): p. 1921-33. PMID: 15155180
- Prutsky, G., et al., Treatment outcomes of human bartonellosis: a systematic review and meta-analysis. Int J Infect Dis, 2013. 17(10): p. e811-9. PMID: 23602630
- Please identify as Figure 1, Figure 2 etc, and place the image(s) in the PowerPoint presentation being submitted. Please remove patient identifiers (name, medical records number, date, etc.) from each image to protect patient confidentiality.
- Below, please note the type of image (CT scan, MRI, radiograph, physical finding photo, laboratory slide which identifies the specific stain used, etc.) and the legend/findings to accompany the individual figures.
Figure #, location of image, type of image, legend
- Suppurative granulomas from biopsy of right groin lymph node. H&E stain 10x magnification.
- Warthin Starry stain, biopsy of right groin lymph node. 40x magnification (most representative photo)
Please indicate which photo or figure you think is most representative of the case.
A. Lagoo, None
A. W. Baker, None