Cat Scratch Disease

Etiology

The principal etiologic agent of cat scratch disease is B. henselae- a fastidious intracellular gram-negative rod. The infection affects the lymph nodes draining the area of inoculation, usually from a scratch or bite of a young cat. There have been clinical descriptions of cat scratch disease for over 50 years, but the bacteriologic agent was not identified for decades. Dr. Douglas Wear, a pathologist, identified a new bacterium in the lymph nodes of cat scratch patients. This led to decades of research to identify the bacteriologic agent. Initially, there was cross-reactivity between Chlamydia and Bartonella species. After the development of electron microscopy, the Warthin Starry stain was used to detect black spots of the bacteria in affected lymph node specimens. The entity of bacillary angiomatosis in the AIDS era identified Warthin-Starry positive bacteria in the early 1990s and was found to be the same agent as a control group of cat scratch patients.[4][5][6]

Epidemiology

Cat scratch disease typically causes a mild illness in immunocompetent hosts. Fifty-five percent of cases are in children younger than 18 years of age; 60% of these are males. More than one-half occur in September through January in the United States. The distribution is worldwide.

The vector of cat scratch disease are cats that acquire the bacteria from the cat flea (Ctenocephalides felis) bite with subsequent bacteremia. The cat is not symptomatic at the time. B. henselae is difficult to culture but can be detected by serologic or by PCR methods.  Infection may be acquired from scratch, bite, or infected saliva through broken skin. Fifty-six percent of cats with bacteremia are less than 1 year of age.[7]

Pathophysiology

The clinical hallmark is lymphadenopathy at the site of inoculation. In the immunocompetent host, a granulomatous response ensues. The immunocompromised host may develop a vascular-proliferative response. Affected lymph nodes become enlarged and tender over one to two weeks. Cat scratch disease is a common cause of chronic lymphadenopathy as well, which may spread beyond the site of inoculation. Cat scratch disease can disseminate to the eye, liver, spleen, and central nervous system (CNS).

Histopathology

Histological examination of the lymph nodes is characterized by granulomas, classically with microabscesses in the center of the lesion. Similar histologic changes may occur in the inoculation site as well as regional lymph nodes.

History and Physical

Eighty-five percent to 90% of children have self-limited lymphadenopathy accompanied by high fever. Patients with disseminated illness may have a spectrum of complications, especially in the very young, elderly, and immunocompromised hosts such as transplant or patients with HIV. Involved systems may include the cutaneous, lymphatic, and visceral organs. More uncommonly, there may be ocular and neurologic involvement.

Cutaneous manifestations begin as an erythematous papule, vesicle, or nodule, which is known as the primary inoculation lesion. This lesion usually persists from one to three weeks but can last for months. The primary inoculation site may be a mucous membrane such as the conjunctiva that heals without scarring and is not detected. Examination of intertriginous areas, other skin creases as well as the scalp may help demonstrate the primary lesion.

Lymphatic system involvement presents as tender lymphadenopathy, regional, and may be solitary or multiple nodes 1 to 5 cm in diameter. There is overlying erythema. Ten percent may suppurate. The lymph nodes are enlarged proximal to the inoculation site. Common sites are the axillary, epitrochlear, cervical, supraclavicular, or submandibular lymph nodes. The lymphadenopathy may last from 1 to 4 months.

Visceral organ involvement may include the liver, spleen, or both and present with fever, weight loss, and abdominal pain. There may be elevated acute phase reactants and liver function tests. Cat scratch disease may be the cause of up to one-third of children with fever of unknown origin. 

Ophthalmic complications include neuroretinitis, papillitis, optic neuritis, and most commonly Parinaud Oculoglandular syndrome. This is an atypical presentation found in 2% to 8% percent of children, which involves an inoculation site in the conjunctiva. There is local adenopathy, typically preauricular, upper cervical, or submandibular, with severe conjunctival infection. The conjunctival infection resolves in several weeks, but the lymphadenopathy may persist for months. Cat scratch may also cause focal or multifocal retinochoroiditis, panuveitis, branch retinal artery, and vein occlusion, leading to retinal detachment.

Neurologic complications of cat scratch include ataxia, cranial nerve palsies, and a dementia-like picture in older patients. Children typically present with encephalitis or aseptic meningitis. However, status epilepticus has been reported. 

A myriad of musculoskeletal complaints has been associated with cat scratch disease, including arthralgias, myalgias, and frank arthritis.

Evaluation

There may be a presumptive diagnosis of cat scratch disease, given the correct historical and examination findings. B. henselae is difficult to culture. Exposure to cats is usually necessary for diagnosis. Serologic testing may confirm the diagnosis with EIA or IFA; however, negative serologic tests do not rule out the diagnosis. Lymph node biopsy is not indicated routinely but should be considered if the diagnosis is unclear. Historically, excision of affected lymph nodes has been avoided for fear of the development of fistulas. Ultrasound may aid needle aspiration to obtain tissue.[8][9]

Treatment / Management

In mild cases, treatment may not be necessary. Supportive care, including antipyretics and anti-inflammatory medications in addition to warm compresses to the inoculation site, may be all that is needed. In mild to moderate presentation in immunocompetent patients, a course of azithromycin may be indicated. Azithromycin for 5 days has been shown to relieve the pain of severe lymphadenopathy but shown no reduction in the overall duration of symptoms. Azithromycin dose is 10 mg/kg day 1 and 5 mg/kg days 2 to 5. Individuals weighing greater than or equal to 45 kg can receive the adult (maximum) dose of 500 mg day one and 250 mg day 2 through 5. Immunocompromised patients should be treated to help prevent the progression to severe systemic disease. Antibiotic regimens including rifampin, trimethoprim-sulfisoxazole, and ciprofloxacin are available for severe, disseminated disease.[7][10][11](B3)

Differential Diagnosis

Differential diagnoses include causes of acute, subacute, and chronic lymphadenopathy. The differential does include viral agents such as CMV, HIV, and EBV, but these agents usually cause diffuse lymphadenopathy. Skin papules similar to the lesion at the inoculation site may occur in fungal infections, leishmaniasis, and nocardiasis. In immunocompromised hosts, there may be a myriad of infectious agents to consider. The presentations of HIV as bacillary angiomatosis may be confused with Kaposi sarcoma.

Prognosis

In 90 to 95% of children, cat scratch disease will resolve spontaneously with symptomatic control, including analgesics, antipyretics, and warm compresses. In patients with disseminated disease, recovery may take months to a year with morbidities depending on the system involved. The immunocompromised host may have a debilitating course.