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Cat-scratch disease (CSD) is an infectious disease consisting of gradually progressive regional lymphadenopathy, fevers, and malaise often occurring after contact with a feline animal (scratch). Atypical presentations are characterized by a variety of neurologic manifestations as well as granulomatous involvement of the eye, liver, spleen, and bone. The disease is usually self-limiting, and recovery is typically complete; however, patients with atypical presentations, especially if immunocompromised, may suffer significant morbidity and even mortality.
Disease Entity
Disease
There are generally two forms of CSD as it relates to the eye:
- Parinauds Ocularglanduar Syndrome: consisting of lymphadenopathy and follicular conjunctivitis
- Neuroretinitis: consisting of lymphadenopathy and granulomatous inflammation of the retina and optic nerve with classic optic nerve swelling, macular star (neuroretinitis), and possible vasculitis.
Etiology
Major cause: Bartonella henselae, possibly Afipia felis and Bartonella clarrigeiae. Bartonella is excreted in flea feces and is transferred to humans when the the feces gets in contact with humans via trauma from a cat scratch or cat bite. Other modes of transmission/reservoirs are ticks and other animal scratches and bites.
General Pathology
Bartonella species are a gram-negative hemotrophic bacillus.
Pathophysiology
Bartonella organisms typically invade, and colonize mature erythrocytes and or endothelial cells. Endothelial invasion leads to a pro-inflammatory response and vasoproliferation. Systemic and ocular infections are dependent on immune status of the infected individual. CSD acutely manifests with systemic infection including fevers, malaise, anorexia, and lymphadenopathy. These symptoms occur within 1-2 weeks with contact with the infective organism. Unusual manifestations are visceral involvement including endocarditis, bacteremia, osteomyelitis, hepatosplenomegaly, encephalitis, and bacillary angiomatosis. Bacillary angiomatosis is a vascular proliferation in different organs such as the skin and lymph nodes. It was traditionally described in immunocompromised patients but has now been reported in immunocompetent individuals.
Diagnosis
Various laboratory and histological techniques are used to diagnosis an infection with Bartonella. If a biopsy of the specimen is taken then this tissue can be stained for histopathological analysis with Warthin-Starry staining.
Serological testing is used most commonly to diagnosis this disease with either ELISA or indirect fluorescence assay (IFA). The sensitivities and specificities vary with both techniques and the CDC currently prefers IFA test. PCR testing can also be used and can differentiate between different Bartonella species. Additionally, PCR can be used on tissues to aid in diagnosis.
History
Approximately 1-3 weeks after inoculation of the bacteria into the host, regional lymphatic tissues begin to display granulomatous infiltration.
Signs
The most common presentation is regional lymphadenopathy. Pre-auricular, submandibular, or cervical lymph nodes are typically affected. Conjunctival epithelium ulcerations, and necrosis are commonly seen producing a purulent discharge in severe cases. Erythematous overlying skin, showing signs of suppuration from involved lymph nodes. Careful examination; evidence of cutaneous inoculation in the form of a nonpruritic, slightly tender pustule or papule. Parinaud oculoglandular syndrome (conjunctival inflammation with preauricular adenopathy) may be seen in about 2-7% of patients with cat-scratch disease.
Typical intraocular presentations include neuroretinitis with optic nerve edema, macular star formation, and discrete white retinal or choroidal lesions. Vascular leakage from the optic nerve head results in the macular star formation, which may persist for months despite resolution of the neuroretinitis. In more recent studies, discrete white retinal, and chorioretinal lesions were a more common finding than the ‘classic’ macular star, and neuroretinitis. More sight-threatening presentation includes intermediate uveitis, retinal vasculitis, vascular occlusions (artery and venous) , and retinitis. Less common posterior segment findings include granulomas, choroiditis, angiomatoisis lesions, and local serous retinal detachments.
Symptoms
Patients typically present with unilateral decline in vision (20/80) with systemic symptoms present in 67%. Unilateral conjunctival injection, foreign body sensation, and epiphora may be present. Malaise and headache occur in fewer than one third of patients.
Others may present with a scotoma if the optic nerve is involved.
Clinical diagnosis
Typical history of prodromal symptoms, lymphadenopathy, and cat exposure helps strengthen the diagnosis, especially when presenting in young adults or children. It more commonly presents in the younger ages in the late summer and fall months.
Diagnostic procedures
Visual field testing sometimes shows cecocentral scotoma. Fluorescein angiography often shows optic nerve leakage or can show artery/venous occlusions.
Optical coherence tomography (OCT) can display the degree of subretinal fluid, retinal thickening, and exudates. OCT angiography may be able to show neovascularization within an area of chorioretinitis.
Although rarely required, in the presence of typical presentation and blood titers, lymph node biopsy or culture may be performed.
- Biopsy: classically shows granulomatous inflammation. Warthin-Starry silver stain on biopsy can identify the bacteria.
- Culture: B. henselae is a fastidious, slow-growing, gram-negative rod that requires specific culture techniques for tissue or blood such as up to 1 month incubation period, enriched agar with 5% CO2 at 32-35 degrees Celsius.
Laboratory test
Serologies: An IFA or ELISA Bartonella serology (titer ≥1:64) is diagnostic. A PCR assay on tissue or blood is also available.
Routine laboratory findings: Mild leukocytosis or leukopenia, infrequent eosinophilia and elevated ESR or CRP. Abnormalities of bilirubin excretion and elevated hepatic transaminases are usually secondary to hepatic obstruction by granuloma, mass, or lymph node. In patients with neurologic manifestations, lumbar puncture usually reveals normal CSF, although there may be a mild pleocytosis and modest elevation in protein.
Differential diagnosis
Etiologies that must be differentiated include other causes of optic nerve head swelling such as optic neuritis, and sarcoid papillitis. Also, infectious etiologies such as syphilitic perineuritis, and rarely toxoplasmosis can produce a similar clinical appearance. Pseudotumor cerebri can mimic the less frequent appearance of bilateral CSD. Lyme disease, Rocky Mountain Spotted Fever, toxoplasmosis, toxocariasis, histoplasmosis, and leptospirosis may also cause neuroretinitis.
Granulomas of this syndrome must be differentiated from those associated with:
- Tularemia
- Tuberculosis or other myobacterial infections
- Brucellosis
- Sarcoidosis
- Sporotrichosis or other fungal diseases
- Toxoplasmosis
- Lymphogranuloma venereum
- Benign and malignant tumors such as lymphoma
Management
CSD tends to be a self-limiting disease. Treatment is dependent on age, immune status, systemic manifestations, and ocular complications.
General treatment
Antipyretics and NSAIDs may also be used. Warm compresses to the affected nodes. In cases of encephalitis or coma, antibiotics and supportive care are indicated.
Medical therapy
Doxycycline (100 mg twice daily) has good intraocular, and central nervous system penetration. However, in patients less than 12 years of age, erythromycin is recommended due to the risk of tooth discoloration. Azithromycin has been observed to cause rapid resolution of lymphadenopathy. However, the distribution of azithromycin to the eye appears higher for conjunctival tissue but lower in intraocular fluids. Corticosteroids are also a consideration for both systemic and ocular therapy. Intravitreal anti-VEGF therapy has been used for the treatment of choroidal neovascularization as well as macular edema in the setting of CSD.
Prognosis
Visual improvement can vary based on the initial ophthalmic manifestation. In Habot-Wilner et al. at last follow up in 79 eyes 80% of eyes had good vision (vision better than 20/40), 14% had moderate vision loss (20/40-20/200), and 6% had severe vision loss (worse than 20/200). In this series more patients had retinal or choroidal lesions. In one review looking at optic nerve involvement, final vision was better or equal to 20/40 in 68% of eyes and worse than 20./200 in 5.7% of eyes.
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