In an otherwise healthy child or young adult with recent cat scratch, papular lesion, tender regional lymphadenopathy and low‑grade fever, what is the most likely diagnosis and how should it be initially managed?

Cat Scratch Disease: Initial Encounter and Treatment

Most Likely Diagnosis

In an otherwise healthy child or young adult presenting with recent cat exposure, a papular lesion at the scratch site, tender regional lymphadenopathy, and low-grade fever, the diagnosis is cat scratch disease (CSD) caused by Bartonella henselae. 1, 2

Clinical Presentation to Confirm Diagnosis

• A papule or pustule develops 3-30 days after the cat scratch or bite at the inoculation site 2, 3
• Regional lymphadenopathy appears approximately 3 weeks after the initial scratch, typically involving nodes draining the scratch site (axillary for arm scratches, epitrochlear/axillary for hand scratches, inguinal for leg scratches) 2, 3
• Low-grade fever, malaise, and fatigue are common systemic symptoms 1
• The lymph nodes are typically tender, firm, and may become suppurative in approximately 10% of cases 2, 3

Initial Management Algorithm

Step 1: Immediate Wound Care (If Presenting Acutely After Scratch)

• Thoroughly cleanse the scratch with soap and water or sterile normal saline immediately to reduce bacterial inoculation 1
• Assess tetanus immunization status and update if needed 1

Step 2: Determine Need for Treatment

For typical, uncomplicated CSD in immunocompetent patients, treatment with azithromycin is recommended to accelerate lymph node resolution, though the disease is self-limited. 4, 1, 2

Treatment is strongly indicated for:

• Immunocompromised patients (especially HIV with CD4+ <100 cells/µL) 2
• Extranodal or disseminated disease (hepatosplenic involvement, neuroretinitis, encephalopathy, osteomyelitis) 2, 5
• Severe or persistent symptoms 4

Step 3: Antibiotic Selection and Dosing

First-line treatment: Azithromycin 4, 1, 2

• For patients ≥45.5 kg (100 lb): 500 mg orally on day 1, then 250 mg once daily for 4 additional days (total 5 days) 4, 1, 2
• For patients <45.5 kg: 10 mg/kg orally on day 1, then 5 mg/kg once daily on days 2-5 4, 1, 2

Alternative regimens if azithromycin is contraindicated: 2

• Doxycycline: 100 mg twice daily for 10-14 days (adults); 2.2 mg/kg twice daily for children, maximum 100 mg per dose 1, 2
• Erythromycin: 500 mg four times daily 2

Step 4: Diagnostic Testing (When Needed)

Clinical diagnosis is sufficient for typical presentations with clear cat exposure history. 1, 2

Order serologic testing when:

• Clinical presentation is atypical (no documented scratch, unusual location of lymphadenopathy) 3, 6
• Extranodal disease is suspected 3
• Immunocompromised patient requires confirmation 3
• Differential diagnosis includes tuberculosis, lymphoma, or other serious conditions 6

Critical caveat: Serologic testing may be negative if performed <6 weeks after infection, and up to 25% of HIV patients with CD4+ <100 cells/µL never develop antibodies despite active infection 2, 3

Evidence Supporting Azithromycin

The recommendation for azithromycin is based on the only placebo-controlled trial in CSD, which demonstrated that lymph node size regressed by 80% at 30 days significantly more frequently in azithromycin-treated patients compared to placebo (P = 0.02) 4. While CSD is self-limited and resolves within 1-6 months without treatment 2, 3, azithromycin accelerates resolution and is particularly beneficial for symptomatic patients.

Red Flags Requiring Escalation

• Persistent fever without localizing signs suggests possible bacteremia and warrants blood cultures and consideration of hospitalization 2
• Neurologic symptoms (encephalopathy, seizures, altered mental status) indicate CNS involvement requiring urgent evaluation and treatment with doxycycline with or without rifampin 2, 7
• Visual changes suggest neuroretinitis or stellate retinopathy requiring ophthalmologic evaluation 7, 8
• Hepatosplenic involvement (abdominal pain with low-density lesions on imaging) may require gentamicin for severe cases 2, 5, 6
• Immunocompromised patients risk bacillary angiomatosis (red papular vascular lesions) requiring prolonged treatment (>3 months) with erythromycin or doxycycline 4, 2

Follow-Up Instructions

• Advise patients to return if signs of worsening infection develop: increasing pain, redness, swelling, purulent drainage, or fever 1
• Lymphadenopathy typically resolves within 1-6 months; persistent nodes beyond this warrant re-evaluation 2, 3
• Monitor for suppuration of lymph nodes, which occurs in 10% of cases and may require needle aspiration (not incision and drainage) 2

Common Pitfalls to Avoid

• Do not use penicillins or first-generation cephalosporins—they have no in vivo activity against Bartonella 2
• Do not test cats for Bartonella infection—this provides no diagnostic or management benefit 2
• Do not confuse CSD with infected cat scratch requiring amoxicillin-clavulanate—the latter is for acute wound infection with Pasteurella multocida, not CSD 1
• Do not perform lymph node biopsy routinely—reserve for atypical presentations where malignancy or tuberculosis cannot be excluded clinically 6
• Do not use doxycycline in pregnant women—erythromycin is the only safe option during pregnancy 2