What could be the cause of fever, body pain, headache, and leucopenia (low white blood cell count) lasting for 1 week?

Differential Diagnosis: Fever, Body Pain, Headache, and Leucopenia for 1 Week

The most likely diagnoses to consider urgently are dengue fever, ehrlichiosis, or Crimean-Congo hemorrhagic fever (CCHF), with dengue being the most common globally and requiring immediate diagnostic workup with PCR/NAAT testing and complete blood count monitoring. 1, 2

Immediate Diagnostic Approach

Priority Testing

• Order dengue PCR/NAAT immediately if symptoms are within 1-8 days of onset, as this is the most sensitive diagnostic test during the acute phase 1, 2
• Obtain complete blood count with differential to assess the degree of leucopenia, platelet count, and hematocrit levels 1, 2
• Check liver enzymes (AST/ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) as elevations are highly specific for certain viral hemorrhagic fevers 3
• Blood cultures should be obtained before antibiotics if bacterial infection cannot be excluded 4

Critical History Elements

• Recent travel history to tropical/subtropical areas or endemic regions for dengue, malaria, or tick-borne diseases 4, 1
• Mosquito or tick exposure within the past 4-8 days for dengue or 1-2 weeks for ehrlichiosis 4, 1
• Medication history including recent beta-lactam antibiotics (penicillins, cephalosporins) which can cause leucopenia after 14+ days of high-dose therapy 5
• Presence of rash, bleeding manifestations, or retro-orbital pain which strongly suggest dengue 4, 1

Most Likely Diagnoses Based on Clinical Pattern

Dengue Fever (Most Common Globally)

Dengue presents with fever, headache, retro-orbital pain, myalgia, arthralgia occurring 4-8 days after mosquito exposure, with leucopenia and thrombocytopenia being characteristic findings. 1, 2

• Clinical features: Frontal headache, retro-orbital pain, muscle and joint pain, rash 4, 1
• Laboratory findings: Leucopenia, thrombocytopenia (≤100,000/mm³), elevated hematocrit indicating plasma leakage 4, 1, 2
• Timing: Symptoms typically appear 4-8 days post-exposure 1
• Warning signs requiring hospitalization: Persistent vomiting, abdominal pain, mucosal bleeding, lethargy, rising hematocrit with falling platelets 1, 2

Ehrlichiosis (Tick-Borne)

Ehrlichiosis presents as acute febrile illness with headache, myalgia, and rigors, with characteristic laboratory findings of leucopenia, thrombocytopenia, and elevated liver enzymes. 4

• Clinical features: Acute onset fever, headache, myalgia, rigors, malaise 4
• Laboratory findings: Leucopenia, thrombocytopenia, elevated ALT/AST 4
• Diagnostic test: IFA antibody titer or PCR assay; intracytoplasmic morulae may be visible in leukocytes 4
• Geographic distribution: Upper midwest and northeast (HGE) or southeastern US (HME) 4

Crimean-Congo Hemorrhagic Fever

CCHF presents with fever, headache, widespread body pain, fatigue, nausea, vomiting, with highly specific laboratory findings of leucopenia, thrombocytopenia, elevated CK, AST/ALT, and LDH. 3

• Clinical features: Fever, headache, widespread body pain, fatigue, nausea, vomiting 3
• Laboratory findings: Leucopenia, thrombocytopenia, elevated CK, AST/ALT, LDH levels 3
• Risk factor: Tick exposure in endemic regions 3
• High mortality rate: Requires urgent recognition and supportive care 3

Malaria (If Travel to Endemic Area)

Malaria should be considered in any febrile patient with travel to endemic areas, presenting with fever, myalgias, and potentially leucopenia, though thrombocytopenia and anemia are more characteristic. 4

• Clinical features: Fever, myalgias, headache 4
• Diagnostic test: Blood smear for parasites or rapid diagnostic test 4
• Timing: Symptoms typically within 2 weeks to months after exposure 4

Drug-Induced Leucopenia

Beta-lactam antibiotics administered parenterally in high doses for ≥14 days can cause leucopenia, requiring close monitoring of white cell counts. 5

• Risk factors: High-dose parenteral penicillin or cephalosporin therapy for ≥14 days 5
• Management: Discontinue beta-lactam antibiotic; do not switch to another beta-lactam as cross-reactivity may occur 5

Parvovirus B19

Parvovirus B19 can cause prolonged febrile illness with leucopenia, neutropenia, and thrombocytopenia in healthy adults, though this is less common. 6

• Clinical features: Prolonged intermittent fever 6
• Laboratory findings: Leucopenia, neutropenia, thrombocytopenia with normal hemoglobin 6
• Diagnostic test: Parvovirus B19 IgM/IgG serology and viral DNA detection 6

Immediate Management Priorities

If Dengue Suspected (Most Common Scenario)

• Aggressive oral hydration: Encourage 2-3 liters of oral fluids daily 1, 2
• Acetaminophen only for fever: Avoid aspirin and NSAIDs completely due to bleeding risk 1, 2
• Daily monitoring: CBC with platelets and hematocrit daily for first 3-5 days 1, 2
• Hospitalization criteria: Any warning signs (persistent vomiting, abdominal pain, mucosal bleeding, lethargy, rising hematocrit, falling platelets <100,000/mm³) 1, 2

If Bacterial Infection Cannot Be Excluded

In patients with fever and neutropenia (absolute neutrophil count <500/mm³), empirical broad-spectrum antibiotics must be initiated within 2 hours of presentation. 4

• Antibiotic choice: Antipseudomonal beta-lactam (cefepime, piperacillin-tazobactam, or carbapenem) 4
• Do not delay: Infection can progress rapidly in neutropenic patients 4
• Blood cultures first: Obtain before antibiotics if possible 4

If Severe Disease or Shock Present

• Immediate fluid resuscitation: 20 mL/kg isotonic crystalloid bolus over 5-10 minutes 1, 7
• Vasopressor support: If hypotension persists after two fluid boluses, initiate norepinephrine 7
• ICU admission: Required for dengue shock syndrome or severe manifestations 4, 1

Critical Pitfalls to Avoid

• Never use aspirin or NSAIDs when dengue or other viral hemorrhagic fever cannot be excluded due to increased bleeding risk 1, 2
• Do not dismiss elevated hematocrit as polycythemia vera in acute febrile illness; this represents hemoconcentration from plasma leakage in dengue 2
• Do not delay antibiotics if bacterial infection is possible and patient has neutropenia (ANC <500/mm³) 4
• Do not switch between beta-lactam antibiotics if drug-induced leucopenia is suspected, as cross-reactivity may worsen the condition 5
• Do not discharge patients with warning signs even if they appear stable, as dengue can rapidly progress to shock 1, 2