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Bartonella infection in children Rabeen Lutchman Why this talk O Think outside the box Structure O Quick Revision of an Approach to lymphadenopathy Bartonella: O Organism and different species O Etiology and Pathogenesis O Epidemiology O Clinical Picture of typical Cat Scratch Disease O Atypical Presentation O Diagnosis O Treatment Case Presentation Lymphadenopathy O Infection, Inflammatory and Malignant processes O Generalized – 2 or more non-contagious lymph nodes groups O Regional – 1 lymph node group O Pathological is more than 10mm (15mm inguinal) Generalized Lymphadenopathy O Viral EBV, CMV, HIV, Hepatitis(B,C), Varicella, Adenovirus, Rubella O Bacterial Mycobacterium Tuberculosis, Treponema Pallidum (secondary syphilis), Brucella, Leptospira interrogans O Fungal Histoplasma capsulatum Coccidioides immitis O Protozoal Toxoplasma gondi Regional Lympadenopathy O STDs Neisseria gonorrhoese Treponema pallidum Herpes simples virus Haemophilus ducreyi Chlamydia trochomatis O Non Venereal Origin Bacterial Staphylococcus aureus Group A and B Streptococci Mycobacterium tuberculosis Bartonella henselae Yersinia pestis Sporothrix schenckii O Viral EBV O Protozoal Toxoplasma gondii Non infectious lymphadenopathy O Congenital O Inflammatory conditions (JIA, SLE, Kawasaki’s Disease) O Malignancy (leukemia,lymphoma,neuroblastoma) O Adverse drug reactions (phenytoin, INH, allopurinol) Batonella Infection in Children Organism O gram-negative, intracellular, oxidase- negative, fastidious aerobic rods. O Warthin –Starry silver impregnation stain or Brown –Hopps tissue Gram-stain. Species Etiology and Pathogenesis O Cats O Direct horizontal transmission ✗ O Ctenocephalides felis O Evasion of the immune system - intraerythrocytic parasites O Humans cat saliva or scratch of a cat. O Invades CD34 hematopoietic progenitor cells and not the erythrocytes directly O Presence and Replication of these organisms inside erythroid differentiated cells Response Immune Competent Host: O Granulomatous and Suppurative O Lymphoid hyperplasia and arteriolar proliferation O Interferon- y- mediated T helper1 cell response macrophage recruitment O Multinucleated giant cells with central areas of necrosis O Microabsesses ± suppuration of the lymph node O Remains within the lymphatics O Symptomatic response lasting 2-4 months Immune Deficient Host: O Vasoproliferative response O Bacillary angiomatosis O Differential : Kaposi’s or pyogenic granuloma or verruca peruana (B bacilliformis) Epidemiology O Worldwide distribution (not confined to O O O O developing countries) Overall seroprevalence in cats in the US 28 -51% Disease of children 54- 87% of cases with CSD being under 18 0.6 per 100 000 children < 18 years 0.86 per 100 000 children < 5 years High Rate of Bartonella henselae infection in HIV-positive outpatients in Johannesburg, South Africa - Frean et al., Trans Royal Soc. Trop Med. Hyg., 2002;96:549-550 O 188 pts – 19 (10.1%) were PCR positive for B hensaelae O 1 patient had suspected bacillary angimatosis O 13 of the 19 were tested serologically and 8/13 (62%) were seropositive (1:64 or higher) Clinical Manifestations Typical Cat Scratch: O O O O O O O Isolated lymphadenopathy with fever ( ⅓ may present without fever and <10% have a fever > 39°C) Erythematous papule - 3 to 10 days after inoculation Erythematous, vesicular and papular crusted stages Regional lymphadenopathy 1-3 weeks after inoculation Lymphadenopathy is seen in all with typical CSD and 85% have a single node involved – most commonly axillary and epitrochlear (46%) and the head and neck (26%) and inguinal (17.5%) Nodal distribution contact most commonly with the hands ± 10% of nodes will suppurate drainage Non typical or complications of B. hensalae infection Pyrexia of unknown origin O Reported cases 3rd most common after EBV and osteomyelitis O ± 30 %hepatosplenic involvement O intra abdominal lymphadenopathy with fever and abdominal pain O PUO and abdominal pain Ocular manifestations: O O O O O O O O O Neuroretinitis and macular stellate exudate is the most common posterior segment ocular complication Stellate macular retinopathy has been associated with several infections including CSD Approximately 2/3 of patients with neuroretinitis have positive serological evidence of previous B. henselae infection Unilateral or rarely bilateral abrupt loss of vision Optic disc swelling and macular star formation Recovery of vision within 2-3 months Optimal treatment for the neuroretinitis is unknown – doxycycline and rifampicin in adults for 4-6 weeks good results Other posterior segment presentations : panuveitis, retinal vasoproliferative lesions, macular hole, vitreal detachment, retinal white spots and a papilitis In immunocompromised patients: subretinal mass with an abnormal vascular network – best seen with fluorescein angiography Other : O Encephalopathy O Haematological O Hepatosplenic – with abdominal lymphadenopathy and microabscesses in the spleen (Not all TB!!) O Dermatological - Bacillary angiomatosis O Orthopedic – osteomyelitis/osteolytic lesions. O RF negative arthritis/ arthralgia (female/adults/erythema nodosum) (mainly knees/wrist/ankle and elbow joints) O Pulmonary – atypical pneumonia/ pleural thickening/ effusion O Pseudomalignancy Diagnosis Treatment O Varies : clinical manifestation and immune status of the patient O Paucity of data – most case series rather than RCA’s O Divide between in vitro efficacy of antibiotics and the ability to successfully treat in clinical practice O In vitro sensitive to macrolides/aminoglycosides/ trimethroprimsulphamethoxazole /B lactams and extended spectrum cephalosporins/ rifampicin and ciprofloxacin Single RCA : Prospective randomized double-blind placebocontrolled evaluation of azithromycin for the treatment of cat-scratch disease. Pediatr infect Dis J. 1998;17(6): 447-452 80% decrease in lymph node volume in 50% of AZA treated patients compared to 7% of the placebo group in the first 30 days O No difference in clinical outcome and no efficacy demonstrated for disseminated disease O O Aspiration if the suppurate or if chronic O O O O large painful lymphadenopathy I and D ✗ chronic sinus tract formation Complicated management is guided case studies rather than RCA’s For neuroretinitis doxycycline is considered a preferred drug because of the intraocular and CNS penetration . Children less than 8 ? ? antibiotic is necessary Case Study O 3 year old girl referred from the clinic with non resolving conjunctivitis not responding to chloromycetin eye drops O Seen in Ggr: 1 week history of red eyes, photophobia and poor vision – walking into objects O On examination: lymph nodes palpated in the anterior chain of cervical region (small nodes) and (R) red eye O Referred to opthalmology… Differential macular star Workup HIV Θ RPR/ FTA Abs Θ Toxo IgG/IgM Θ Toxocara canis IgG Elisa Θ ESR 27 ANA Θ ds DNA Θ ASOT Θ CT brain: No features of ICP, Impression of slight optic nerve swelling ?Neuritis otherwise unremarkable orbits and retro orbital structures O LP: cells Θ, Bacteria Θ, VDRL/FTAΘ, Crpto/ CLATΘ O Bartonella serology pending Rx: Azitromycin 5 days and Bactrim for 6 weeks O O O O O O O O O References 1. 2. 3. 4. 5. Todd et al. Beyond cat scratch disease: widening spectrum of Bartonella henselae infection. Pediatrics May 2008; 121(5):e1413-1425 Tsukahara et al. Bartonella henselae infection as a cause of fever of unknown origin. Journal of Clinical Microbiology.2000,38(5):1990-1991 Ahmad M et al.Seroprevalence of Bartonella henselae and Bartonella quintana infections in children from Central and Northern Jordan Saudi Med J 2004; Vol.25(11): 1664-1669 Bass et al. Prospective randomized double-blind placebocontrolled evaluation of azithromycin for the treatment of cat-scratch disease. Pediatr infect Dis J. 1998;17(6): 447452 Frean et al. High Rate of Bartonella henselae infection in HIV-positive outpatients in Johannesburg, South Africa. Trans Royal Soc. Trop Med. Hyg., 2002;96:549-550