Pain Behind the Eyes: Differential Diagnosis of Leptospirosis, West Nile Virus, and Dengue Fever
Direct Answer
Retro-orbital pain (pain behind the eyes) is a classic feature of dengue fever and should prompt immediate diagnostic testing, while it is not a characteristic feature of West Nile virus or leptospirosis. 1, 2, 3
Clinical Differentiation
Dengue Fever (Most Likely)
Dengue fever characteristically presents with fever, headache, retro-orbital pain, myalgia, arthralgia (particularly back pain), and rash, with an incubation period of 4-8 days. 1, 2, 3
- Retro-orbital pain occurs in approximately 18-94% of dengue cases and is a distinguishing feature. 3
- Conjunctival injection (redness) is present in approximately 39% of cases. 3
- The rash typically appears during days 3-7 of illness, coinciding with defervescence. 4
- Fever is universal (100% of cases). 3
Leptospirosis (Less Likely for Retro-Orbital Pain)
Leptospirosis presents with headache, fever, chills, and musculoskeletal pain, but retro-orbital pain is NOT a characteristic feature. 5, 6
- Transmitted through contact with urine of infected animals or contaminated water/soil. 6
- Can be difficult to distinguish from dengue in endemic areas. 6
- Approximately 5-10% develop severe disease with 5-15% case-fatality rate in severe cases. 6
West Nile Virus (Least Likely for Retro-Orbital Pain)
West Nile virus primarily causes encephalitis rather than retro-orbital pain. 1
- Classified as an arbovirus causing encephalitis as its primary severe manifestation. 1
- Does not characteristically present with retro-orbital pain. 1
Diagnostic Algorithm
For Patients with Retro-Orbital Pain and Fever:
Step 1: Immediate Testing (Days 1-7 of symptoms)
- Order dengue PCR/NAAT on serum for patients with symptoms for 1-7 days. 2, 7
- Obtain complete blood count to assess for thrombocytopenia (present in 69.51% of dengue cases) and leucopenia (20.19% of cases). 3
- Check liver transaminases (elevated in 88.54% of dengue cases). 3
Step 2: If PCR Negative or Symptoms >7 Days
- Order IgM capture ELISA if PCR is unavailable or negative for patients with symptoms for more than 5-7 days. 2, 7
- IgM antibodies typically develop during the first week and remain detectable for 2-3 months. 7
Step 3: Consider Leptospirosis Only If:
- History of exposure to contaminated water, soil, or animal urine. 6
- Absence of typical dengue features (retro-orbital pain, rash, conjunctival injection). 3
- Perform leptospirosis serology if clinical suspicion exists. 5
Critical Warning Signs Requiring Hospitalization
Patients with dengue and any of the following require immediate hospitalization: 2
- Persistent vomiting
- Abdominal pain or tenderness
- Mucosal bleeding
- Lethargy or restlessness
- Rising hematocrit (>20% increase from baseline) with falling platelet count
- Thrombocytopenia ≤100,000/mm³ with rapid decline
- Narrow pulse pressure ≤20 mmHg or hypotension
Management Based on Diagnosis
If Dengue Confirmed:
Acetaminophen at standard doses is the ONLY recommended analgesic; NEVER use aspirin or NSAIDs due to increased bleeding risk. 2
- Ensure aggressive oral hydration with >2500ml daily. 2
- Monitor CBC daily during critical phase (days 3-7) to track platelet counts and hematocrit. 2
- Patients without warning signs can be managed as outpatients with daily monitoring. 2
If Leptospirosis Confirmed:
Early administration of penicillin G or doxycycline reduces duration and severity of illness. 6
- Intravenous hydration with sodium chloride 0.9%. 5
- Early antibiotic treatment is critical for reducing morbidity and mortality. 6
Common Pitfalls to Avoid
- Never prescribe antibiotics empirically for dengue fever without evidence of bacterial co-infection (occurs in <10% of cases), as this contributes to antimicrobial resistance without clinical benefit. 2
- Never rely solely on clinical presentation to exclude dengue in the post-acute phase; serological confirmation is required. 7
- Never interpret a negative IgM result in the early phase (<7 days) as definitive exclusion, as this may reflect sampling before antibody development. 7
- Never use aspirin or NSAIDs when dengue cannot be excluded. 2
Special Considerations
Pregnant women with suspected dengue require hospitalization and testing by NAAT for both dengue and Zika virus due to risk of maternal death, hemorrhage, preeclampsia, and vertical transmission. 2, 7
- Acetaminophen remains the safest analgesic option for pregnant women. 2
- Cross-reactivity with other flaviviruses (yellow fever, Japanese encephalitis, tick-borne encephalitis) complicates serological diagnosis. 7
Ophthalmologic Examination
Perform dilated fundus examination in patients with severe dengue, as ocular abnormalities including retinal capillary occlusion, vascular sheathing, retinal hemorrhages, and cotton wool spots can cause permanent visual loss. 8