A Case of Parinaud Oculoglandular Syndrome in Which Bartonella DNA Was Detected in the Cornea and Conjunctiva by Polymerase Chain Reaction.

Background and Objectives: Parinaud oculoglandular syndrome (POS) is unilateral granulomatous follicular conjunctivitis with ipsilateral afferent lymphadenopathy, primarily caused by cat-scratch disease, tularemia, and sporotrichosis. We report a case of POS in which Bartonella DNA was detected using polymerase chain reaction (PCR) in corneal and conjunctival specimens. Methods: A 29-year-old man, who started keeping a stray cat two months prior, became aware of right preauricular lymphadenopathy and right ocular conjunctival hyperemia one month prior. Subsequently, he developed a fever of approximately 37.9 °C, with a purulent ocular discharge appearing 1 week before being referred to our department for a detailed ophthalmological examination. The patient's right eye showed hyperemia and edema in the bulbar conjunctiva, along with palpebral conjunctival hyperemia, follicles, and white ulcers. Two weeks later, his serum IgM titer for Bartonella henselae was 1:20, and Bartonella DNA was detected by PCR in the corneal and conjunctival specimens. Based on these findings, the patient was diagnosed with POS caused by cat-scratch disease (CSD). Oral doxycycline, rifampicin, topical gatifloxacin, betamethasone phosphate, and erythromycin eye ointments were prescribed. Results: After 2 weeks of oral treatment and 2 months of eye drop treatment, the deterioration of the cornea and conjunctiva improved when the patient recovered good visual acuity. Conclusions: PCR assays of corneal and conjunctival specimens are useful for the diagnosis of CSD presenting with POS. These results suggested that Bartonella may be directly involved in the ocular surface pathogenesis of POS.

Detection of Bartonella henselae in feline erythrocytes in Egypt by using Giemsa staining, transmission electron microscopy, and polymerase chain reaction.

Bartonella species (Bartonella spp.) have gained recognition as a significant human pathogen, implicated in a wide range of diseases. Among these, Bartonella henselae infection has been extensively studied for its primary occurrence in cats and its role in the development of cat-scratch disease in humans. While light microscopy and transmission electron microscopy (TEM) have traditionally played crucial roles in identifying causative agents of infectious diseases, including Bartonella spp., the accuracy of these methods in identifying Bartonella spp. remains undefined. Therefore, this study aims to bridge this gap by employing both light microscopy and TEM to detect Bartonella in feline blood samples and to confirm B. henselae with polymerase chain reaction (PCR). Examination of blood smears stained with Giemsa and toluidine blue semithin sections by using light microscopy revealed the presence of intraerythrocytic corpuscles, suggesting Bartonella infection in six out of 33 examined cat blood samples. TEM findings corroborated these observations, showcasing the engulfment of bacteria by the erythrocyte membrane, along with the presence of some Bartonella spp., adhering to the erythrocyte wall. PCR-based molecular detection confirmed the presence of B. henselae in these six samples. It is concluded that light microscopy and TEM are considered valuable in the screening of cats' blood for the potential presence of Bartonella. However, further molecular techniques are essential for precise identification and confirmation of specific Bartonella spp. RESEARCH HIGHLIGHTS: Giemsa-stained blood smear and semithin section showed potential intraerythrocytic Bartonella spp. corpuscles. TEM demonstrated the engulfment of Bartonella spp. by the erythrocyte membrane, along with the presence of some Bartonella spp. adhering to the erythrocyte wall. Molecular analysis of blood samples from cats by PCR unveiled that six out of 33 (18.18%) samples tested positive for B. henselae infection.

Three-Month History of Lymphadenopathy Caused by Bartonella henselae in a 13-Year-Old Following a Dog Scratch.

We reported the case of a 13-year-old immunocompetent boy presenting with a right cervical neck mass. He complained of fatigue, back pain, coughing, and a right neck mass persisting for three months. He did not have a fever, but his parents reported he had lost 20 lbs. in the past six months without any change in diet or appetite. They are also very concerned about the risk of malignancy. During the initial work-up, there was no abnormality in the complete blood count. During the follow-up visit 10 days later, he complained of new-onset dysphagia and throat pain. The mass was about 5 cm on the right neck, poorly mobile, and mildly tender to palpation. It looks significantly different compared to the first visit. Blood serology tests were indicated, and titers of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and toxoplasma were not reactive. However, serology detected that IgM and IgG titers to Bartonella henselae were ≥1:20 and ≥1:1024, respectively. A fine needle aspiration (FNA) of the mass on the same day revealed lymphoid proliferation. Afterward, the patient was treated with amoxicillin-clavulanic acid for two weeks. After three weeks, the mass almost disappeared, and the patient reported a remarkable improvement in symptoms. This case report is a helpful reminder that B. henselae should be suspected on the differential diagnoses in a case of lymphadenopathy associated with non-specific symptoms such as fatigue, back pain, and weight loss.

Multifocal Osteomyelitis in an Adolescent Patient With Cat Scratch Disease.

Cat scratch disease (CSD) typically presents as a self-limiting lymphadenopathy associated with a cat bite or scratch and commonly affects children and young adults. Atypical manifestations, involving the eyes, nervous system, heart, liver, spleen, skin, and musculoskeletal system, could be severe and difficult to diagnose, and they could occur in 5%-20% of the cases. Herein, we report an unusual case of CSD with multifocal osteomyelitis. A 15-year-old girl presented with right axillary lymphadenopathy. Since she had a history of cat scratch, azithromycin was started for CSD. Two days later, she was readmitted to our hospital with severe back pain which required differential diagnosis. Lumbar spinal magnetic resonance imaging (MRI) revealed multifocal vertebral osteomyelitis. The patient was hospitalized, and then teicoplanin and cefotaxime were added to the azithromycin therapy. After excluding the possible other causes, the definitive diagnosis of osteomyelitis secondary to CSD was made upon the combination of the MRI scan findings of the vertebrae, histopathological investigation of excisional right axillary biopsy, positron-emission tomography/computed tomography (PET/CT), and Bartonella henselae serologies. Atypical manifestations of CSD are widely variable; therefore, it should be kept in mind in the differential diagnosis of severe musculoskeletal pain and osteomyelitis.

Parinaud Oculoglandular Syndrome Among Female Adults in Malaysia: A Case Series.

Parinaud oculoglandular syndrome (POGS), is typically rare and often presented as a unilateral ocular inflammation accompanied by ipsilateral lymphadenopathy. POGS is an atypical manifestation of cat scratch disease (CSD) caused by Bartonella henselae (BH). Diagnosis of POGS poses a challenge due to its rarity and the array of potential etiologies including infections from fleas, ticks, and various microorganisms. This case series details three cases of CSD attributed to POGS, highlighting the diagnostic challenges faced in the absence of the gold standard diagnostic method, which is the polymerase chain reaction (PCR) DNA test for BH. The cases encompass a set of presentations including granulomatous inflammation and lymphadenopathy, managed effectively with antibiotics and non-pharmacological interventions such as flea control in domestic felines and hygiene measures post-feline inflicted injury. These cases highlight the necessity for heightened clinical suspicion, especially in patients with a history of feline contact, and appeal for further research to refine diagnostic criteria for more accurate and practical detection of CSD particularly for the atypical manifestations. This will be especially beneficial in areas where the more invasive lesion biopsy or gold standard PCR DNA test for BH are not available so accurate management can be instituted immediately in cases where there is multisystemic involvement.

Bartonella Neuroretinitis with Initial Seronegativity and an Absent Macular Star: A Case Report and Literature Review.

Cat-scratch disease (CSD) is an infectious disease caused by Bartonella henselae, presenting with fever and lymphadenopathy following contact with felines. The ocular manifestations include neuroretinitis, characterised by optic nerve swelling and a macular star. Case Presentation: We discuss a case of neuroretinitis that presented atypically, without a macular star. There was an initial suspicion of Bartonella, but the serology was negative. Our patient was eventually empirically treated for infective neuroretinitis based on a positive contact history (recently scratched by one of his three pet cats). There was progression to a macular star upon serial dilated fundus examination, and the repeated serology one week after symptom onset showed rising titres, supporting a diagnosis of CSD. Conclusions: A judicious review of systems, repeat assays, serial dilated fundus examination, and early ophthalmic evaluation are useful in cases of suspected neuroretinitis, remaining an important differential in the evaluation of sudden-onset painless vision loss and unilateral disc swelling.

Atypical Haemorrhagic Presentation of Neuro-Retinitis and Serous Retinal Detachment Secondary to Cat-Scratch Disease.

Cat-scratch disease (CSD) is a self-limited disease caused by Bartonella henselae, a fastidious gram-negative intracellular bacillus bacterium. Neuroretinitis, a form of optic neuropathy characterised clinically by optic disc swelling and a macular star, is an uncommon manifestation of CSD occurring in approximately 1-2% of cases. We report a case of a 14-year-old female who presented to the emergency department with a chief complaint of acute painless vision loss described as a large black spot in the centre of her right eye vision 2 weeks after being scratched by cats. Fundus examination revealed Frisen grade 5 disc oedema with an atypically diffuse disc and peripapillary haemorrhages with associated subretinal fluid and a macular star in the right eye. Optical coherence tomography (OCT) of the macula and retinal nerve fibre layer showed subretinal fluid involving the fovea, a serous retinal detachment of the nasal macula, and significant optic disc oedema in the right eye. The patient was admitted and treated with doxycycline, rifampin, and prednisone taper. After completing the treatment course, the patient's vision improved, fundus examination showed significantly improved disc oedema and haemorrhages, and OCT demonstrated resolution of the subretinal fluid in the right eye.

Cat Scratch Disease Presenting with Right Branch Retinal Artery Occlusion and Left Neuroretinitis.

Introduction: Bartonella henselae, the causative agent of cat scratch disease (CSD), presents with diverse ocular manifestations, posing diagnostic challenges. This study aimed to elucidate the diagnostic complexities through a unique case. Case Presentation: A 42-year-old male presented with vision loss in the right eye, subsequent to flu-like symptoms following exposure to a stray kitten. Clinical examination revealed branch retinal artery occlusion (BRAO) in the right eye and neuroretinitis in the left, indicating concurrent ocular manifestations of CSD. Thorough investigations, including serological testing, ruled out alternative causes, highlighting the rarity of such coexisting ocular complications. Conclusions: The coexistence of BRAO and neuroretinitis in different eyes underscores the variable presentation of CSD. Recognition of infectious etiologies, particularly Bartonella, is paramount in diagnosing ocular vasculopathies. This case emphasizes the importance of considering Bartonella infection in patients with ocular vascular occlusions, especially in the context of recent cat exposure and systemic symptoms suggestive of CSD.

Cat scratch disease unveils hidden breast carcinoma: A diagnostic twist.

Cat scratch disease is a rare condition that can present with different clinical manifestations, including axillary lymphadenopathy. Here, we report the case of a 45-year-old female who presented with axillary lymphadenopathy attributable to a process of differential diagnosis to cat scratch disease. During the thorough investigation of her condition, a routine mammogram was performed, due to the unilateral axillary lymphadenopathy, revealing the presence of previously undiagnosed breast carcinoma in situ; in fact, a DCIS (invasive ductal carcinoma with spread to the ipsilateral axillary nodes) was incidentally found. This case highlights the importance of comprehensive differential diagnosis and a multidisciplinary approach in managing patients with atypical presentations of common diseases, given that other alarming but unrelated findings are visible.

Atypical clinical and sonographic manifestations of lymphadenopathy in a child with cat-scratch disease: A case report.

Cat-scratch disease is a well-known infection in childhood. It usually presents as tender lymphadenopathy and should be included in the differential diagnosis of any lymphadenopathy syndrome. An history of exposure to cats supports the suspect and a positive serologic test to Bartonella henselae confirms the diagnosis. Ultrasound is the first line radiologic imaging performed in case of lymphadenopathy. The presence of hypoechoic lobular or oval mass with central hyperaemia and a possible adjacent fluid collection and surrounding oedema may differentiate the disease from other aetiologies. We describe the case of a 7-year-old girl presenting with an axillary lymphadenopathy, without a reported recent history of exposure to cats, with sonographic findings suggestive for cat-scratch disease. In this case, ultrasound was very useful in orienteering the diagnosis and insist on the medical history. Serology resulted positive for B. henselae and at the end the family remembered that 6 months before the child was scratched by a kitten.

[Cat-scratch disease, clinical features in adults]. / Características clínicas de pacientes adultos con enfermedad por arañazo de gato.

INTRODUCTION: Cat-scratch disease (CSD) is caused by Bartonella henselae and it is under-recognized in adults because it mainly affects children. Clinical course is commonly benign and self-limited; occasionally, there may be systemic involvement. METHODS: Case-series study carried out in a tertiary care hospital in Buenos Aires suburbs. Patients older than 15 years diagnosed with CSD over a 5-year period were included (2016-2021). RESULTS: 30 adult patients were analyzed, with a median age of 20.5 years (IQR 17-29), 73% (n = 22) were male; 96% (n = 27) had history of exposure to cats. The most common clinical presentation of CSD was peripheral lymphadenopathy (90%), the average complication rate was 33% (n = 10), 86.7% (n = 26) received antimicrobial therapy, with a median duration of 5 days (IQR 5-10). Outcome was favorable in 83% (n = 25), 16% (n = 5) were lost to follow-up. DISCUSSION: Clinical features of CSD in adults are poorly described in the worldwide literature. Diagnosis can be challenging because the clinical hallmark is regional lymphadenopathy.

Introducción: La enfermedad por arañazo de gato (EAG) es producida por Bartonella henselae y debido a que afecta principalmente niños, es poco reconocida en adultos. El cuadro evolutivo es generalmente benigno y autolimitado, aunque ocasionalmente puede haber compromiso sistémico. Métodos: Estudio observacional, descriptivo y retrospectivo realizado en un hospital de tercer nivel del conurbano bonaerense. Se incluyeron pacientes mayores de 15 años con diagnóstico de EAG en un período de 5 años (2016-2021). Resultados: Se analizaron 30 pacientes adultos, con una mediana de edad de 20.5 años (17-29), el 73% (n = 22) fueron varones. El 96% (n = 27) presentó contacto estrecho con gatos. La presentación clínica más frecuente fue adenopatías periféricas (90%); el porcentaje de complicaciones fue de 33% (n = 10). La indicación de antibioticoterapia fue de 86.7% (n = 26), con una mediana de duración de 5 días (5-10). La evolución fue favorable en el 83% (n = 25), en el 16% (n = 5) se perdió seguimiento. Discusión: La EAG es poco reconocida en adultos; las características clínicas de este grupo etario se encuentran poco descriptas en la literatura. Es un desafío diagnóstico debido a que su forma de presentación más frecuente es la adenopatía localizada.

First report of Bartonella henselae and Bartonella clarridgeiae carriage in stray cats from Ecuador and its link to a cat scratch disease outbreak in 2022.

INTRODUCTION: The genus Bartonella includes species and subspecies of fastidious, facultative intracellular Gram-negative bacilli that infect a wide variety of mammalian reservoirs including cats and humans. In 2022, the Ecuadorian Ministry of Health reported an outbreak of cat scratch disease caused by B. henselae in the city of Guayaquil. Therefore, we aimed to characterize the presence of Bartonella spp. in domestic and stray cats from the area of Guayaquil where the outbreak happened in 2022. METHODS: Whole blood samples of 100 domestic and stray cats were collected. Riboflavin synthase (ribC) and 16S rRNA genes detection was performed by PCR using Bartonella spp. specific primers, followed by Sanger sequencing and phylogenetic analysis. RESULTS: 14 cats were positive for Bartonella spp. carriage. Phylogenetic analysis confirmed the presence of 12 cats infected with B. henselae and 2 cats with B. clarridgeiae. CONCLUSIONS: There is a high prevalence of Bartonella spp. carriage in cats in the city of Guayaquil within the area where a recent cat scratch disease outbreak happened. Considering the high presence of cats and other domestic and stray animals in the city of Guayaquil, a One Health approach for surveillance and prevention of zoonotic diseases like cat scratch disease is needed.

Development and Diagnostic Potential of a Novel Bartonella henselae-Specific Immunoglobulin.

Bartonella henselae is a gram-negative rod-shaped bacterium and is the primary causative agent of Cat Scratch Disease (CSD). Although the prevalence of CSD is low in the human population, the possibility of developing multi-organ complications, especially in vulnerable individuals, remains a serious cause for concern. The immunofluorescent assay (IFA) is currently one of the most common laboratory tests for the detection of antibodies to B. henselae in serum, however, it has several disadvantages. The enzyme-linked immunosorbent assay (ELISA) technique offers a more quantitative, sensitive, and cost-effective alternative to conventional IFAs. Here, we report the purification of a novel bioidentical polyclonal antibody from discarded human serum for use as a standard in ELISAs against B. henselae. This novel method of antibody production overcomes the many limitations of animal-derived antibodies while also offering a more robust, reproducible, and scalable antibody production alternative for the diagnosis of CSD.

Application of metagenomic next-generation sequencing in the diagnosis of Bartonella neuroretinitis: a case report and literature review.

BACKGROUND: Cat-scratch disease (CSD) is caused by Bartonella henselae infection. In atypical cases of CSD, pathogen determination is challenging. We report a case of Bartonella neuroretinitis with neither a clear history of scratches nor typical general symptoms. The diagnosis was made using metagenomic next-generation sequencing (mNGS), a high-throughput sequencing technology. CASE PRESENTATION: A female patient presented to the ophthalmologist with complaint of blurred vision in her right eye. Although with history of raising a cat, she reported no clear history of scratches or typical general symptoms, except a fever of unknown origin which resolved spontaneously. The best corrected visual acuity (BCVA) of the right eye was count fingers. Fundus examination showed optic disc oedema, macular exudates and inferior exudative retinal detachment. Laboratory examination results showed increased value of serum C-reactive protein and erythrocyte sedimentation rate. Ocular involvement of toxoplasmosis, syphilis and tuberculosis were excluded. To identify the possible causative pathogen of the disease, mNGS of aqueous humour sample was performed and 521 reads of B. henselae were identified. Serological test results further showed a positive immunoglobulin G (IgG) titre of 1:64. Taking the contact history, clinical manifestations, mNGS and serological results into consideration, the diagnosis of Bartonella neuroretinitis (ocular CSD) was made. After appropriate treatment, the BCVA of the right eye improved to 20/25 in the last follow-up. Fundus examination showed a normal optic disc and macula, and the exudates had reduced. CONCLUSION: mNGS, a fast and unbiased method, can be used to detect B. henselae (if present) in intraocular fluid samples.; however, the results should be interpreted together with the clinical symptoms and other auxiliary test results.

Bartonella Henselae Related Unilateral Anterior Uveitis and Subsequent Multifocal Retinitis in a Case Under Certolizumab Treatment.

Introduction: A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. Case description: A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Discussion: Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery. LEARNING POINTS: Anti-tumour necrosis factor treatment is fraught with several ocular side effects including myositis, corneal infiltrates, scleritis, uveitis, optic neuritis, retinal vasculitis and ophthalmoplegia.When a new uveitis episode occurs in cases undergoing anti-tumour necrosis factor therapy, its cause poses a diagnostic challenge as it can have either an infectious or a non-infectious nature.Though very rare, ocular bartonellosis may also occur in immunocompromised individuals and a prompt diagnosis and appropriate treatment can lead to an excellent visual recovery.

Post-COVID reactivation of latent Bartonella henselae infection: a case report and literature review.

Cat scratch disease (CSD) is caused by Bartonella henselae (B. henselae) and presents as lymphadenopathy following close contact with cats. However, in context of the global COVID-19 pandemic, clinical manifestations of CSD may vary, posing new challenges for healthcare professionals. Here we describe a case of a 54-year-old male with painful left upper arm mass, which gradually resolved until he was infected with COVID-19. The mass then rapidly progressed before admission. Meanwhile, pulmonary symptoms including pleural effusion emerged simultaneously. The cause was undetermined with routine blood culture and pathological test until the next generation sequencing (NGS) confirmed the presence of B. henselae. We believe this case is the first to report localized aggravation of CSD after COVID-19 infection and hopefully, offers treatment experience for clinicians worldwide.

Unmasking Bartonella henselae infection in the shadows of long COVID thanks to clinical metagenomics.

The diagnosis of long COVID often relies on symptoms post-COVID-19, occasionally lacking biological evidence. This case study illustrates how investigating long COVID uncovered an underlying bartonellosis through clinical metagenomics. Following mild COVID-19, a 26-year-old woman experienced persistent symptoms during 5 months, including axillary adenopathy. Pathological examination, 16 S rRNA PCR, and clinical metagenomic analysis were done on an adenopathy biopsy. The latter revealed Bartonella henselae DNA and RNA. Treatment with clarithromycin improved symptoms. This case underscores the relevance of clinical metagenomics in diagnosing hidden infections. Post-COVID symptoms warrant thorough investigation, and bartonellosis should be considered in polyadenopathy cases, regardless of a recent history of cat or flea exposures.

Cat Scratch Disease of the Breast/Axilla: Recognition of a Rare Disease and Approaches for Differential Diagnosis.

Cat scratch disease rarely presents as a breast or axillary mass mimicking carcinoma both clinically and radiologically. Diagnosing breast/axillary cat scratch disease is challenging due to its rarity and nonspecific findings. Here, we reported 2 patients with breast cat scratch disease and reviewed 14 patients with cat scratch disease involving breast/axilla from the past 30 years. It mainly affects women (median age: 48), consistently presenting as axillary lymphadenopathy, and demonstrates ipsilateral breast mass in half of patients (50%, 8/16). The breast mass was most commonly located in the upper outer quadrant (88%, 7/8), indicating the possibility of disease extension from axillary adenopathy. Around half of patients (56%, 9/16) reported cat exposure. Histologically, most patients (93%, 14/15) presented as necrotizing granulomas, with characteristic stellate-shaped necrosis in 5 patients. Although pathologic differential diagnoses between cat scratch disease and cancer are straightforward, distinguishing cat scratch disease from other granulomatous mastitis poses diagnostic challenges. Silver stains should be included in the diagnostic workup panel when highly suspecting cat scratch disease clinically. However, they were only able to highlight the causative microorganism in 54% (7/18) patients, and the gram stain was negative in all 12 tested patients. In contrast, polymerase chain reaction (PCR) for the causative microorganism was consistently positive in all 3 tested patients, while serologic test confirmed diagnosis in 85% (11/13) patients; 1 patient with negative serology showed a positive PCR result. Therefore, upfront PCR tests with or without serologic study should be considered to confirm the diagnosis of cat scratch disease in a timely manner.