What is the diagnosis for a patient with fever, chills, body pain, and fatigue of 4 days duration, with a 1 cm lymph node in the neck and lab results showing leukopenia (low white blood cell count) with neutrophilia (elevated neutrophils)?

Differential Diagnosis: Acute Febrile Illness with Leukopenia and Lymphadenopathy

The most likely diagnosis in this patient is a viral infection, with tickborne rickettsial diseases (particularly ehrlichiosis or anaplasmosis) being critical considerations that require immediate empiric treatment if there is any epidemiologic risk, given the potential for severe morbidity and mortality.

Primary Diagnostic Considerations

Viral Syndrome (Most Common)

• The combination of fever, chills, body pain, fatigue, and leukopenia (WBC 3200) with relative neutrophilia (73%) is most consistent with an acute viral infection 1
• The 1 cm cervical lymph node represents reactive lymphadenopathy, commonly seen with viral upper respiratory or systemic viral infections 1
• The leukopenia (WBC 3200) is mild and typical of viral infections, though the neutrophil predominance (73%) is somewhat atypical for most viral syndromes 2, 1

Tickborne Rickettsial Diseases (Critical to Exclude)

• Human monocytic ehrlichiosis (HME) or human granulocytic anaplasmosis (HGA) must be strongly considered, as these present with fever, chills, myalgias, and characteristic leukopenia with relative neutrophilia 3
• The CDC guidelines emphasize that leukopenia (WBC <4.5 x 10^9/L) combined with fever and myalgias should trigger consideration of tickborne rickettsial diseases, even without a history of tick bite 3
• Approximately 60-90% of patients with ehrlichiosis do not recall a tick bite, making absence of this history unreliable for excluding the diagnosis 3
• The presence of lymphadenopathy can occur with ehrlichiosis, though it is not the most common finding 3

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• While the patient has leukopenia rather than eosinophilia, DRESS syndrome can present with fever, lymphadenopathy, and leukopenia in early stages 1
• This diagnosis requires careful medication history review 1

Critical Laboratory Findings Analysis

Leukopenia Assessment

• The WBC count of 3200 cells/µL represents mild leukopenia (normal: 4500-11,000) 4, 5
• The absolute neutrophil count (ANC) can be calculated as: 3200 × (0.73) = 2336 cells/µL, which is within normal range and does NOT represent neutropenia 5
• This mild leukopenia with preserved ANC does not require antimicrobial prophylaxis, as severe neutropenia (ANC <500) is not present 4, 5

Neutrophil Predominance

• The 73% neutrophils with leukopenia is an unusual pattern that is highly characteristic of ehrlichiosis or anaplasmosis 3
• Most viral infections cause lymphocytosis, not neutrophilia, making this finding particularly important 2
• The CDC guidelines note that ehrlichiosis typically presents with leukopenia and a left shift (increased bands), though total neutrophil percentage may be elevated 3

Immediate Diagnostic Workup Required

Essential Initial Tests

• Peripheral blood smear examination looking for morulae (intracellular inclusions) in monocytes (HME) or neutrophils (HGA) 3
• Complete metabolic panel to assess for elevated transaminases (AST/ALT), which occur in 80-90% of ehrlichiosis cases 3
• Platelet count to evaluate for thrombocytopenia, present in 60-90% of ehrlichiosis cases 3
• Blood cultures to exclude bacterial sepsis 3

Specific Diagnostic Tests

• Serologic testing for Ehrlichia chaffeensis and Anaplasma phagocytophilum by IFA (though acute sera are often negative) 3
• PCR testing for ehrlichiosis/anaplasmosis if available (more sensitive in acute phase) 3
• Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serologies for common viral causes 1

Treatment Algorithm

Immediate Empiric Therapy Decision

If the patient has ANY of the following, start doxycycline 100 mg twice daily immediately:

• Geographic location in endemic area (south central, south Atlantic, or upper Midwest United States) 3
• Outdoor activities or potential tick exposure in past 2-3 weeks 3
• Presence of thrombocytopenia or elevated transaminases 3
• Clinical deterioration or severe symptoms 3

Rationale for Empiric Treatment

• The mortality rate for untreated ehrlichiosis ranges from 3-5%, with higher rates in immunocompromised patients 3
• Doxycycline is highly effective when started early and has minimal adverse effects for short-term use 3
• Acute serology is negative in 85% of patients during the first week of illness, so negative initial testing does NOT exclude the diagnosis 3
• Broad-spectrum antibiotics (penicillins, cephalosporins, fluoroquinolones) are NOT effective against rickettsial organisms 3

If Tickborne Disease is Unlikely

• Supportive care with antipyretics and hydration
• Close monitoring for development of warning signs (thrombocytopenia, elevated liver enzymes, altered mental status) 3
• Re-evaluation in 24-48 hours if symptoms persist or worsen 3

Common Pitfalls to Avoid

• Never exclude ehrlichiosis based on absence of tick bite history—most patients do not recall being bitten 3
• Never exclude ehrlichiosis based on absence of rash—only 30% of adults with HME develop a rash 3
• Do not wait for confirmatory serology before starting doxycycline if clinical suspicion exists—acute sera are usually negative 3
• Do not assume the neutrophil predominance rules out infection—this pattern is characteristic of ehrlichiosis 3
• Do not use fluoroquinolones or beta-lactams for empiric coverage if tickborne disease is suspected—these are ineffective 3
• The mild leukopenia (WBC 3200) does NOT require antimicrobial prophylaxis or G-CSF, as the ANC is >2000 4, 5

Geographic and Epidemiologic Context

• Ehrlichiosis is endemic throughout the contiguous United States, with highest incidence in Arkansas, Missouri, Oklahoma, and North Carolina 3
• Anaplasmosis is most common in the upper Midwest and Northeast United States 3
• Peak incidence occurs April through September, corresponding to tick activity 3
• Occupational or recreational outdoor activities increase risk 3