Systemic Cat-Scratch Disease: a "Troublesome" Diagnosis.

Diagnosis of systemic cat scratch disease may be challenging. Here, we describe a case of an immunocompetent girl exhibiting fever and multifocal hepatosplenic abscesses. Diagnostic tests for Bartonella henselae infection (enzyme immunoassay and polymerase chain reaction) were found steadily negative and the diagnosis, suspected on the basis of the Margilet's criteria, was finally confirmed by indirect immunofluorescent antibodies.

Pediatric Bartonella henselae Infection: The Role of Serologic Diagnosis and a Proposed Clinical Approach for Suspected Acute Disease in the Immunocompetent Child.

BACKGROUND: Bartonella henselae serology is commonly used to diagnose cat-scratch disease (CSD). Titers above a threshold for positivity suggest either a recent or remote infection. Recent infection can be confirmed by a 4-fold rise in the convalescent titer in some cases. Many atypical presentations attributed to CSD utilize a low threshold for positivity without supportive evidence from convalescent sera or supplemental testing, raising a concern for the overdiagnosis of CSD. METHODS: We conducted a retrospective chart review of immunocompetent pediatric patients at the Hospital for Sick Children, Toronto, spanning an 11-year period. A total of 154 cases were included with serologic titers ≥1:128. These were divided into 3 groups: group 1 = 1:128, group 2 = 1:256, and group 3 ≥ 1:512. Cases within groups were evaluated with respect to cat contact, clinical presentation, further testing, and final diagnosis. RESULTS: One-third of patients with a titer of 1:128 had an alternative diagnosis. Most cases with a titer of 1:128 or 1:256 did not have convalescent serologic testing performed. Within these 2 groups, only 1 case had a 4-fold rise in the convalescent titer. A trend of decreasing number of cases with alternative diagnoses (P = 0.03) and increasing number of cases presenting with regional lymphadenopathy (P = 0.07) was associated with higher titers in group 3 compared with group 1. CONCLUSION: Concerns about the serologic diagnosis of CSD include the use of low titers for positivity, incomplete diagnostic evaluation, and the lack of convalescent serologic testing. We propose a clinical guide to assist in managing suspected cases of CSD.

Bartonella henselae: evidencia serológica en pacientes pediátricos con sospecha clínica de enfermedad por arañazo de gato / Bartonella henselae: Serological evidence in pediatric patients with clinical suspicion of cat scratch disease

La enfermedad por arañazo de gato (EAG) es producida por Bartonella henselae.Afecta principalmente a ninos y el reservorio es el gato doméstico. El diagnóstico de laboratorio se basa en la detección de anticuerpos por inmunofluorescencia indirecta (IFI). El objetivo de este trabajo fue analizar la evidencia serológica de infección por B. henselae en pacientes pediátricos que reunían criterios clínicos/epidemiológicos para la sospecha de EAG. Se estudió a 92 pacientes; de acuerdo con los resultados serológicos, estos fueron categorizados en 4 grupos: 1) IgG (+)/IgM (+), 31,5% (n = 29);2) IgG (-)/IgM (+), 10,9% (n = 10);3) IgG (+)/IgM (-), 9,8% (n = 9), y 4) IgG (-)/IgM (-), 47,8% (n = 44). La divulgación de estos resultados intenta promover futuros trabajos que investiguen la seroprevalencia de Bartonella spp. en Argentina. Esto permitirá conocer la importancia de esta zoonosis en nuestra población y evaluar nuevos puntos de corte para esta técnica serológica.

Cat scratch disease (CSD) is caused by Bartonella henselae, which mainly affects children. The cat is the reservoir. The laboratory diagnosis is based on the detection of antibodies by the Indirect Immunofluorescence (IFI) assay. The objective of this study was to analyze the serological evidence of B. henselae infection in pediatric patients that met the clini-cal/epidemiological criteria for suspected CSD. We studied 92 patients, who were categorized into four serological groups: 1) IgG (+)/IgM(+), 31,5% (n = 29); 2) IgG (-)/IgM(+), 10,9% (n = 10); 3) IgG (+)/IgM(-), 9,8% (n = 9); 4) IgG (-)/IgM(-), 47,8% (n = 44). These findings aim to promote future works for investigating the seroprevalence of Bartonella spp. in Argentina, which will allow us to know the importance of this zoonosis in our population and to evaluate new cut-off points of the technique.

Development of a Specific and Sensitive Enzyme-Linked Immunosorbent Assay as an In Vitro Diagnostic Tool for Detection of Bartonella henselae Antibodies in Human Serum.

Bartonella henselae causes cat scratch disease and several other clinical entities. Infections with B. henselae are frequently occurring; however, the infection is only rarely diagnosed, mainly due to a lack of knowledge in the medical community. Microscopic immunofluorescence assays (IFA) are widely used for the serodiagnosis of B. henselae infections but are laborious and time-consuming, and interpretation is subjective. An easy and reliable method for the serological diagnosis of B. henselae infections is needed to overcome the shortcomings of the current IFA. Here, we report the development of an ELISA detecting human anti-B. henselae antibodies from serum samples. By separating the water-insoluble fraction of B. henselae Houston-1 via ion-exchange chromatography, 16 subfractions were generated and tested for immunoreactivity via line blotting. One particular fraction (fraction 24) was selected and spotted on ELISA plates using an industrial production platform. By use of well-characterized human sera from the strictly quality-controlled serum library of the German National Consiliary Laboratory for Bartonella infections, the sensitivity of this ELISA was 100% for PCR-proven infections and 76% for clinically suspected infections at a specificity of 93%. This ELISA is therefore a reliable high-throughput method allowing the serodiagnosis of B. henselae infections.

Cat Scratch Disease in a 1.5-year-old girl - Case report.

INTRODUCTION: The paper is a case report presenting Cat Scratch Disease (CSD) in a 1.5-year- old girl. Bartoneloses, including CSD, are a group of infectious diseases which are rarely detected, therefore there are no statistical data concerning the aetiology, and the incidence of CSD noted in Poland is low in comparison with other European countries. OBJECTIVE: The purpose of the paper is to discuss several problems related to CSD. MATERIAL AND METHODS: A 1.5-year-old girl who was seen in hospital for the sparing use of her left arm when crawling. X-rays showed osteolytic lesions which radiologists described as multi-ocular cyst or infection. As neither clinical examination nor laboratory investigations found pathological signs, the patient was followed-up on an ambulant basis. Repeated x-ray taken 4 weeks later showed increased periosteal proliferation accompanied by pain. The baby was admitted to the Clinic but additional investigations found no pathologies. The baby was consulted by a rheumatologist and haematologist; however, they did not facilitate a definitive diagnosis. As the baby developed, because of a thickening of the soft tissues on the dorsal side of the distal epiphisis in the forearm the doctors decided to inspect the condition operatively. Macroscopic examination found brownish granulated tissue. Suction drainage was inserted and a tissue sample was tested for aerobic and anaerobic bacteria, tuberculosis and borelliosis. The test results were negative. The baby was in good condition, was not pyrexial and suffered from less pain. The diagnostics was further expanded and the baby tested for yersinia, chlamydia, tuberculosis and bartonella, i.e. CSD. The postoperative wound healed soon and radiological bony lesions began to resolve. After a month, we received a positive bartonella test result, the baby tested positively for Bartonella henselae IgG class, which confirmed past or active infection of CSD. A repeated test for B. henselae taken 6 months later showed a lower level of antibodies. CONCLUSIONS: It should be remembered that CSD, which is an extremely rare infection, can be diagnosed despite mediocre clinical and radiological manifestations. Thus, in the case of infections of unexplained aetiology and mediocre manifestations diagnostics should include testing for Bartonella henselae.

[Bartonella henselae: Serological evidence in pediatric patients with clinical suspicion of cat scratch disease]. / Bartonella henselae: evidencia serológica en pacientes pediátricos con sospecha clínica de enfermedad por arañazo de gato.

Cat scratch disease (CSD) is caused by Bartonella henselae, which mainly affects children. The cat is the reservoir. The laboratory diagnosis is based on the detection of antibodies by the Indirect Immunofluorescence (IFI) assay. The objective of this study was to analyze the serological evidence of B. henselae infection in pediatric patients that met the clinical/epidemiological criteria for suspected CSD. We studied 92 patients, who were categorized into four serological groups: 1) IgG (+)/IgM(+), 31,5% (n=29); 2) IgG (-)/IgM(+), 10,9% (n=10); 3) IgG (+)/IgM(-), 9,8% (n=9); 4) IgG (-)/IgM(-), 47,8% (n=44). These findings aim to promote future works for investigating the seroprevalence of Bartonella spp. in Argentina, which will allow us to know the importance of this zoonosis in our population and to evaluate new cut-off points of the technique.

Ptosis, miosis and cats.

Horner's syndrome (HS) is caused by a disruption in the oculosympathetic pathway. Both congenital and acquired HS are unusual in children. Acquired HS can be caused by trauma, surgical intervention, tumours, vascular malformations or infection.We describe the case of a 6-year-old boy who was brought to our emergency department with ptosis, miosis, painful cervical lymphadenopathy and a cat scratch on a hand. The diagnosis of a cat scratch disease was confirmed by serology. A full recovery was observed on antibiotic treatment and cervical lymphadenomegaly reduction 3 weeks later.

Seroprevalence of Bartonella henselae in patients awaiting heart transplant in Southern Italy.

BACKGROUND: Bartonella henselae is the etiologic agent of cat-scratch disease. B. henselae infections are responsible for a widening spectrum of human diseases, although often symptomless, ranging from self-limited to life-threatening and show different courses and organ involvement due to the balance between host and pathogen. The role of the host immune response to B. henselae is critical in preventing progression to systemic disease. Indeed in immunocompromised patients, such as solid organ transplant patients, B. henselae results in severe disseminated disease and pathologic vasoproliferation. The purpose of this study was to determine the seroprevalence of B. henselae in patients awaiting heart transplant compared to healthy individuals enrolled in the Regional Reference Laboratory of Transplant Immunology of Second University of Naples. METHODS: Serum samples of 38 patients awaiting heart transplant in comparison to 50 healthy donors were examined using immunfluorescence assay. RESULTS: We found a B. henselae significant antibody positivity rate of 21% in patients awaiting heart transplant (p = 0.002). There was a positive rate of 8% (p > 0.05) for immunoglobulin (Ig)M and a significant value of 13% (p = 0.02) for IgG, whereas controls were negative both for IgM and IgG antibodies against B. henselae. The differences in comorbidity between cases and controls were statistically different (1.41 ± 0.96 vs 0.42 ± 0.32; p = 0.001). CONCLUSIONS: Although this study was conducted in a small number of patients, we suggest that the identification of these bacteria should be included as a routine screening analysis in pretransplant patients.

Malaltia per esgarrapada de gat: un repàs / Enfermedad por arañazo: un repaso / Cat-scratch disease: a review

Fonament: la serologia específica permet comprovar que la malaltia per esgarrapada de gat pot presentar un ventall clínic ample, tot i que la majoria de pacients cursen un quadre clínic típic de lesió dèrmica al lloc d'inoculació, adenopatia regional i febre. Per als casos típics i per a la majoria de casos que hom considera atípics, o amb complicacions, la involució espontània és el fet més probable. Objectiu: recordar les característiques clíniques de les formes atípiques d'aquesta malaltia, que només afecten una minoria de pacients, i el diagnòstic i el tractament de les formes típiques, que són les més habituals. Mètode: revisió bibliogràfica, tant de sèries de casos com de les nombroses notes clíniques publicades. Resultats: més enllà del quadre clínic típic, la malaltia per esgarrapada de gat pot provocar una síndrome de febre perllongada, compromís hepatoesplènic, compromís pulmonar (pneumònia, pleuritis), renal (glomerulonefritis), osteoarticular (osteomielitis), neurològic (encefalitis), dèrmic (diversos exantemes), hemàtic (anèmia hemolítica, púrpura trombocitopènica), ocular (conjuntivitis fol•licular). El compromís cardíac (endocarditis) és greu. En el pacient immunocompromès, la malaltia pot assolir més gravetat. La clínica i la serologia són les formes de diagnòstic més útils. En el cas de malaltia típica, sense complicacions, d'un pacient sense compromís immunitari, el tractament antibiòtic és motiu de controvèrsia: la recomanació acadèmica, que no n'indica cap, s'oposa a la pràctica, que sol indicar azitromicina. Conclusions: s'ha de considerar aquest diagnòstic en més situacions clíniques que les típiques d'adenopatia, febre i antecedent de contacte amb un gat

Fundamento. La serología específica permite comprobar que la enfermedad por arañazo de gato puede presentar amplia variedad clínica, aunque la mayoría de pacientes cursan un cuadro clínico típico de lesión dérmica en el lugar de inoculación, adenopatía regional y fiebre. Para los casos típicos y para la mayoría de los casos considerados atípicos, o con complicaciones, la involución espontánea es el hecho más probable. Objetivo. Recordar las características clínicas de las formas atípicas de esta enfermedad, que sólo afectan a una minoría de pacientes, y el diagnóstico y el tratamiento de las formas típicas, que son las más habituales. Método. Revisión bibliográfica, tanto de series de casos como de las numerosas notas clínicas publicadas. Resultados. Más allá del cuadro clínico típico, la enfermedad por arañazo de gato puede provocar un síndrome de fiebre prolongada, compromiso hepatoesplénico, compromiso pulmonar (neumonía, pleuritis), renal (glomerulonefritis), osteoarticular (osteomielitis), neurológico (encefalitis), dérmico (diversos exantemas), hemático (anemia hemolítica, púrpura trombocitopénica), ocular (conjuntivitis folicular). El compromiso cardíaco (endocarditis) es grave. En el paciente inmunocomprometido, la enfermedad puede presentar más gravedad. La clínica y la serología son las formas de diagnóstico más útiles. En el caso de enfermedad típica, sin complicaciones, de un paciente sin compromiso inmune, el tratamiento antibiótico es motivo de controversia: a la recomendación académica, que no indica antibiótico, se le opone la práctica, que suele indicar azitromicina. Conclusiones. Se debe considerar este diagnóstico en más situaciones clínicas que las típicas de adenopatía, fiebre y antecedente de contacto con un gato (AU)

Background. The availability of a serological diagnosis for catscratch disease has allowed for the description of its wide range of clinical features, although most patients (90%) present with the typical form of the disease, an erythematous lesion at the site of inoculation, regional lymphadenopathy, and fever. In all patients with the typical form of the disease, and in most of those with atypical or complicated presentation, spontaneous resolution is likely. Objective. To review the clinical manifestations of patients presenting with atypical cat-scratch disease, and to review the diagnosis and treatment in those presenting with its typical form. Method. A literature review of case reports and published studies. Results. Beyond the typical clinical presentation, cat-scratch disease can also manifest with prolonged fever of unknown origin, hepatosplenomegaly, pneumonia or pleural thickening or effusion, glomerulonephritis, osteomyelitis, encephalitis, skin rash, hemolytic anemia, thrombocytopenic purpura, endocarditis, and oculoglandular syndrome (follicular conjunctivitis). Immunocompromised individuals may develop severe disease. The key to diagnosis is a careful history and serological testing. In immunoclícompetent patients with typical clinical manifestations and no complications, antibiotic therapy is controversial; although published studies have shown little or no effect, in clinical practice azithromycin is often prescribed. Conclusions. Cat-scratch disease should be considered in the differential diagnosis of more clinical scenarios than the typical presentation of regional lymphadenopathy and fever after contact with a ca (AU)

[Bartonella henselae in children with regional adenitis treated in a Peruvian national hospital, 2012]. / Bartonella henselae en niños con adenitis regional atendidos en un hospital nacional del Perú, 2012.

In order to determine the frequency of seropositive cases of Bartonella henselae in children with regional adenitis treated in a national hospital in Peru, a cross-sectional study was conducted in 106 children with regional adenitis greater than 1 cm in diameter. The sample was selected from patients aged 5-11 years seen at the National Institute of Child Health for acute onset of regional adentitis, with more than five days of symptoms. B. henselae seropositivity was defined by indirect immunofluorescence test. We found that 86 children (81.1%) were positive for B.henselae. The median age of the patients was 7 years. In the bivariate analysis, the following associated factors were found: aged 5 years, history of fever, lymphadenopathy greater than 4 cm and reported contact with cat. In conclusion, children with regional adenitis treated in this national referral hospital showed a high frequency of positive serology for B. henselae.

Bartonella henselae en niños con adenitis regional atendidos en un hospital nacional del Perú, 2012 / Bartonella henselae in children with regional adenitis treated in a Peruvian national hospital, 2012

Con el objetivo de determinar la frecuencia de casos seropositivos a Bartonella henselae en niños con adenitis regional atendidos en un hospital nacional del Perú, se realizó un estudio trasversal en 106 niños con adenitis regional mayor de 1 cm de diámetro, de aparición aguda, con tiempo de enfermedad mayor de cinco días, atendidos en el Instituto Nacional de Salud del Niño durante el año 2012. Se definió seropositividad para B. henselae mediante el examen de inmunofluorescencia indirecta, siendo positivos 86 niños (81,1%) con una mediana de edad de 7 años, rango de 5 a 11; en el análisis bivariado se encontraron como factores asociados, edad mayor de 5 años, antecedentes de fiebre, adenopatía mayor de 4 cm y reporte de contacto con gato. En conclusión, los niños con adenitis regional atendidos en este hospital de referencia nacional presentaron una frecuencia alta de serología positiva para B. henselae.

In order to determine the frequency of seropositive cases of Bartonella henselae in children with regional adenitis treated in a national hospital in Peru, a cross-sectional study was conducted in 106 children with regional adenitis greater than 1 cm in diameter. The sample was selected from patients aged 5-11 years seen at the National Institute of Child Health for acute onset of regional adentitis, with more than five days of symptoms. B. henselae seropositivity was defined by indirect immunofluorescence test. We found that 86 children (81.1%) were positive for B.henselae. The median age of the patients was 7 years. In the bivariate analysis, the following associated factors were found: aged 5 years, history of fever, lymphadenopathy greater than 4 cm and reported contact with cat. In conclusion, children with regional adenitis treated in this national referral hospital showed a high frequency of positive serology for B. henselae.

Development of an enzyme-linked immunosorbent assay for Bartonella henselae infection detection.

UNLABELLED: Several serological diagnostics rely on enzyme-linked immunosorbent assay (ELISA) to detect bacterial infections. However, for some pathogens, including Bartonella henselae, diagnosis still depends on manually intensive, time-consuming assays including micro-immunofluorescence, Western blotting or indirect immunofluorescence. For such pathogens, there is obviously still a need to identify antigens to establish a reliable, fast and high-throughput assay (Dupon et al. ). We evaluated two B. henselae proteins to develop a novel serological ELISA: a well-known antigen, the 17-kDa protein, and GroEL, identified during this study by a proteomic approach. When serum IgG were tested, the specificity and sensitivity were 76 and 65·7% for 17-kDa, respectively, and 82 and 42·9% for GroEL, respectively. IgM were found to be more sensitive and specific for both proteins: 17-kDa protein, specificity 86·2% and sensitivity 75%; GroEL, specificity 97·7% and sensitivity 45·3%. IgM antibodies were also measured in lymphoma patients and patients with Mycobacterium tuberculosis infection to assess the usefulness of our ELISA to distinguish them from B. henselae infected patients. The resulting specificities were 89·1 and 93·5% for 17-kDa protein and GroEL, respectively. Combining the results from the two tests, we obtained a sensitivity of 82·8% and a specificity of 83·9%. Our work described and validated a proteomic approach suitable to identify immunogenic proteins useful for developing a serological test of B. henselae infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A reliable serological assay for the diagnosis of Cat Scratch Disease (CSD) - a pathological condition caused by Bartonella henselae infection - has not yet been developed. Such an assay would be extremely useful to discriminate between CSD and other pathologies with similar symptoms but different aetiologies, for example lymphoma or tuberculosis. We investigate the use of two B. henselae proteins - GroEL and 17-kDa - to develop a serological-based ELISA, showing promising results with the potential for further development as an effective tool for the differential diagnosing of B. henselae infection.

A case report of seronegative cat scratch disease, emphasizing the histopathologic point of view.

Cat scratch disease, necrotizing granulomatous lymphadenitis caused by Bartonella henselae, usually benign and self-limited. However, various clinical manifestations and no pathognomonic histopathologic features can lead to misinterpretations and diagnostic disputes. We report a case of cat scratch disease in a 39-yr-old male patient with fever and left axillary lymphadenitis. He had a history of cat bite on the left hand dorsum. On excision, the lymph node showed follicular hyperplasia, stellate microabscesses with a rim of granulomatous inflammation. Warthin-Starry silver staining showed many clumps of silver-stained bacilli within the necrotic foci. Serological tests were negative. Diagnosis was established by PCR analysis. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1877499238123059.

Pulmonary nodules in an immunocompetent child with cat scratch disease.

We describe an immunocompetent child with cat scratch disease and pulmonary nodules as part of her initial presentation. Although pulmonary manifestations have been reported with cat scratch disease, nodules are rare in the normal host.

Bartonella henselae infection of prosthetic aortic valve associated with colitis.

The diagnosis of infective endocarditis can be difficult, particularly with atypical presentation and negative blood cultures. A 61-year-old man with a porcine aortic valve presented with fever, intermittent confusion, diarrhea, and fatigue. In the community clinic setting, a colonoscopy performed for anemia demonstrated colitis. Symptoms progressed for months; elicitation of a history of significant kitten exposure and the finding of an axillary lymph node prompted testing for Bartonella henselae antibodies. High titer antibodies by indirect immunofluorescence assay indicated chronic B. henselae infection. Surgical valve replacement followed by prolonged doxycycline and rifampin led to cure. This case illustrates the complexities of infective endocarditis and is the first description B. henselae endocarditis associated with colitis in an immunocompetent adult.

Combining cytomorphology and serology for the diagnosis of cat scratch disease.

Cat scratch disease (CSD) is a self limited zoonotic disease that presents most commonly as a regional lymphadenopathy. We are reporting a case of a 25-year-old male patient who presented with fever and large right inguinal lymphadenopathy. The diagnosis of cat scratch disease was confirmed based on the characteristic cytopathological features on aspirate smears from the lymph node and the serological titers for Bartonella henselae. This case report emphasizes the importance of combining Bartonella serology, and cytopathology in the diagnostic work-up of febrile lymphadenopathy and suspected CSD since the culture of this organism is arduous.

Identification of candidate proteins for the diagnosis of Bartonella henselae infections using an immunoproteomic approach.

Bartonella henselae is an emerging gram-negative facultative intracellular pathogen transmitted via Ctenocephalides felis (cat fleas) or cat scratches. Bartonellosis is present mainly in the form of cat scratch disease (CSD), bacillary angiomatosis and infective endocarditis (IE). The methods used to diagnose B. henselae rely on culturing, immunofluorescent assays and molecular techniques. The objective of the present study was to identify candidate proteins for the serodiagnosis of bartonellosis with the differential discrimination of both clinical scenarios: CSD and IE. For this, an immunoproteomic approach combined with 2-DE, immunoblotting and matrix-assisted laser desorption/ionization time-of-flight MS has been developed. Immunoproteomic profiles of sera collected from patients with CSD and IE were compared with those of blood donors. We identified several candidate proteins as phage-encoding Pap31 protein and an outer membrane protein of BH11510 that, in our view, might be useful for the serodiagnosis of bartonellosis.