Cat scratch syndrome: symptoms and treatment

Cat-scratch disease is a bacterial infection typically characterized by a subacute fever with enlargement of one or more lymph nodes in the drainage area of a cat scratch or bite. The causative agent is Bartonella henselae, an intracellular Gram-negative bacterium. In most immunocompetent individuals, the disease is self-limited, with symptoms resolving within a few weeks. However, in some patients, atypical localizations of infection and dissemination are possible. [1]

The traditional "classic" core of symptoms includes a small papulopustular lesion on the skin at the site of inoculation, which appears several days after the injury, and regional lymphadenitis, which develops 1-3 weeks later. Fever is low-grade or moderate. Contact with a kitten often precedes the disease. These characteristics are reflected in clinical leaflets for the public and physicians. [2]

Although the disease is known to be benign, it is important to remember the rare but clinically significant complications: damage to the eye (neuroretinitis, Parenaud's oculoglandular syndrome), liver/spleen (hepato-/splenic granulomas), bones, central nervous system, and endocarditis. The risk of complications is higher in people with immunodeficiencies (for example, in advanced HIV infection), but they also occur in immunocompetent individuals. [3]

From a public health perspective, CSD is more common in children and adolescents and in regions/seasons with flea activity in cats. This is due to the ecology of the pathogen: B. henselae circulates among cats, and cat fleas (Ctenocephalides felis ) play a key role in maintaining bacteremia in them. [4]

How is it transmitted and who is at risk?

The primary route of transmission is a scratch or bite from a domestic or stray cat (usually a kitten). Transmission occurs when claws or teeth contaminated with flea feces damage human skin. The risk also increases when licking an open wound with the saliva of an infected animal. Direct transmission to humans via flea bites is suspected, but has not been proven. [5]

Cats become infected by fleas and often remain clinically uneventful, while still excreting bacteria; bacteremia is particularly common in kittens. Therefore, contact with young animals and/or lack of flea control is a risk factor. Veterinary recommendations for ectoparasite control for cats themselves also reduce the risk to humans. [6]

In humans, CSD is most often diagnosed in children under 15 years of age. US statistics indicate a seasonal pattern (fall-winter), which coincides with the dynamics of flea activity and contact with kittens. These epidemiological observations assist in initial diagnosis and preventive counseling for families. [7]

Classic "risk situations": playing with young cats, keeping multiple animals without regular flea treatment, household bites/scratches without subsequent antiseptic treatment, and caring for stray cats. In immunocompromised groups (HIV, chemotherapy, transplantation), any scratches require increased attention and early medical attention. [8]

Symptoms: typical and "atypical"

The typical onset is a small papule/pustule at the site of contact (often unnoticed by the time of the visit), followed by an enlarged, painful lymph node (axillary, cervical, or elbow, depending on the location of the scratch) and low-grade fever/febrile temperature after 1-3 weeks. The skin over the node may be warm and reddened; fluctuation sometimes occurs. General well-being is moderately affected. [9]

"Atypical" forms include lesions of the eyes (neuroretinitis, Parenaud's oculoglandular syndrome - conjunctival granuloma + preauricular lymphadenitis), liver and spleen (painful hepato-/splenic nodules, fever of unknown origin), bones (osteitis/osteomyelitis), skin (nodules/angiomatosis in immunocompromised individuals), as well as neurological manifestations (encephalitis, seizures, ataxia). These variants require more active diagnostics and therapy. [10]

A rare but crucial scenario is endocarditis (often culture-negative in blood): in cases of unexplained fever, embolism, or vegetations in people with contact with cats, Bartonella should be considered and molecular methods should be used (including on remote valves). A mistake is to spend too much time searching for "staphylococcus" when cultures are negative and not consider bartonellosis. [11]

In children, CSD is a common cause of prolonged lymphadenitis and fever of unknown origin. However, the severity of symptoms does not always correlate with the size of the node: large nodes may be relatively benign, while small ones can be very painful. This allows for individualized decisions regarding puncture/analgesia. [12]

Diagnosis: What is the diagnosis based on?

In "classic" cases, the diagnosis is clinical: characteristic exposure (cat/kitten), papule at the site of inoculation, regional lymphadenitis, and exclusion of other causes. There is no specific "rapid test" in the laboratory; studies are needed to confirm and exclude mimics. [13]

Blood/material cultures for Bartonella are insensitive, and the culture grows slowly (the laboratory must be notified to hold the cultures for ≥21 days and provide appropriate conditions). Therefore, serology (ELISA/EIA) is the primary method of testing: it is effective, but cross-reactions with other Bartonella species and prolonged persistence of antibodies after infection are possible. Negative serology does not rule out the diagnosis. [14]

PCR for B. henselae is more informative on lymph node aspirate/biopsy material than on blood. However, node aspiration is not routinely required if the diagnosis is clear and there is no need for anesthesia or to exclude alternatives (e.g., atypical mycobacteria/lymphoma). If endocarditis is suspected, PCR is performed on valve tissue. [15]

Instrumental methods are used according to indications: abdominal ultrasound for fever and pain (search for hepato-/splenic foci), neuroimaging for neurological symptoms, and ophthalmological examination for visual complaints. In unclear cases, a biopsy of the node with histological examination (granulomas with microabscesses) and silvering (Warthin-Starry) supports the diagnosis. [16]

Differential diagnosis

In children and adolescents, CSD must be differentiated from staphylococcal/streptococcal lymphadenitis, atypical mycobacteria (eg, M. avium complex; most commonly cervical nodes), toxoplasmosis, infectious mononucleosis (EBV/CMV), and lymphatic tumors. A history of exposure to a cat is helpful but not definitive. [17]

In ocular forms, differentiation is made from herpetic/chlamydial conjunctivitis and other causes of anterior uveitis/neuroretinitis. In neurological manifestations, differentiation is made from viral encephalitis, autoimmune encephalitis, and post-infectious syndromes. A team of ophthalmologists and neurologists is essential. [18]

In cases of fever of unknown origin with abdominal pain, purulent foci of other origin, oncological and inflammatory bowel diseases are excluded. In immunocompromised patients, a wide range of opportunistic infections are considered, including Bartonella angiomatosis and peliosis hepatis. [19]

Suspicion of endocarditis requires searching for the causes of the “culture-negative” variant (including Bartonella, Coxiella burnetii ), using advanced molecular diagnostics and high-resolution echocardiography. [20]

Treatment: When to observe and when to treat

In most immunocompetent patients with uncomplicated lymphadenitis, symptomatic therapy (rest, NSAIDs/analgesics, local heat) and observation are sufficient: the disease resolves spontaneously. Antibiotic intervention remains a subject of debate. [21]

If the lymph node is very painful/large, azithromycin for 5 days can be considered - it accelerates the reduction in node volume (shown in RCTs), although it does not shorten the overall duration of the disease. Recommended doses: adults and children >45.5 kg - 500 mg on the 1st day, then 250 mg/day for another 4 days; children ≤45.5 kg - 10 mg/kg on the 1st day, then 5 mg/kg/day for another 4 days. [22]

For atypical/disseminated forms (eye, liver/spleen, bones, central nervous system) or in immunocompromised patients, antibacterial therapy is indicated. Regimens vary, often using doxycycline ± rifampicin for several weeks; in severe cases, aminoglycosides may be used initially, with adjustments based on clinical symptoms and tolerability. Options and rationale are discussed with an infectious disease specialist/based on specialist recommendations. [23]

Fine-needle aspiration of a fluctuating lymph node is acceptable for pain relief and sample collection, but routine incision/drainage is avoided due to the risk of fistula and scarring; repeat aspiration is possible if the lymph node relapses. The decision is made on an individual basis. [24]

Special situations: eye, nervous system, endocarditis

For neuroretinitis/oculoglandular syndrome, treatment includes antibacterial drugs; the addition of a short course of steroids is decided by an ophthalmologist and infectious disease specialist, based on an adequate antibacterial regimen. The prognosis is usually favorable with early treatment. [25]

Encephalitis/seizure syndrome requires hospitalization, supportive care, and an anti -Bartonella regimen; a neurologist is often involved. Early diagnosis improves outcomes and shortens the duration of fever/neurological symptoms. [26]

Suspected endocarditis ( B. henselae is one of the reasons for "culture-negative") requires long-term combination antibacterial therapy and, if indicated, cardiac surgery; molecular verification on valve tissue significantly improves accuracy. Long "empirical" courses without taking Bartonella into account can delay diagnosis. [27]

In HIV/transplant patients, longer courses and more frequent monitoring during treatment are acceptable, as the risk of relapse and dissemination is higher. Guidelines for opportunistic infections and experienced centers can help select a safe regimen. [28]

Forecast and observation

Most immunocompetent patients have an excellent prognosis: nodules and systemic symptoms resolve within weeks; some experience scarring/moderate nodule tenderness for months. Complications are rare and respond well to treatment with appropriate management. [29]

After an infection, antibodies can persist for a long time, which is important to remember when interpreting serology (a positive ELISA does not mean an "active process"). The decision to repeat antibacterial therapy should be made by a physician based on the combined clinical and instrumental examination data. [30]

Reasons for a return visit: persistent fever >7-10 days, increasing tenderness/fluctuation of the node, the appearance of neurological, visual, or abdominal symptoms, as well as deterioration of well-being in patients at risk. These are situations when a wait-and-see approach without an in-person assessment is unsafe. [31]

In ophthalmological and neurological forms, the recovery period can last for weeks or months; the monitoring program is agreed upon with relevant specialists (ophthalmologist/neurologist) and includes follow-up examinations/visualization as indicated. [32]

Prevention: How to reduce the risk

Avoid scratches, bites, and licking wounds—especially from kittens and stray animals. Wash any scratch or bite immediately with soap and water. Children are taught the rules of safe play with cats (do not tease, do not take food from the animal, do not pull the tail, etc.). [33]

The key measure is flea control in cats: regular veterinary treatments, keeping animals indoors, and avoiding contact with stray cats. For people with immunodeficiencies, it is advisable to avoid keeping kittens under 1 year of age and to carefully maintain hygiene when caring for the animal. [34]

"Prophylactic" antibacterial therapy for humans after any scratch is not recommended, and routine testing/treatment of healthy cats for Bartonella is not recommended —it does not reduce the risk to the owner. Instead, consider hand and environmental hygiene, regular flea treatment, and monitoring the pet's well-being. [35]

It is helpful for families to be aware of the typical signs of CSD and the 'red flags' of complications (visual impairment, severe headaches/meningeal symptoms, severe abdominal pain with fever, signs of heart failure with prolonged fever) - if these occur, urgent medical evaluation is necessary.[36]