What are the differential diagnoses for dengue fever in adults?

Differential Diagnosis of Dengue Fever in Adults

When evaluating an adult with suspected dengue fever, the CDC explicitly recommends considering chikungunya, Zika virus, malaria, rubella, measles, hepatitis A, parvovirus, adenovirus, enterovirus, leptospirosis, rickettsiosis, and group A streptococcal infections in your differential diagnosis. 1

Primary Infectious Disease Differentials

Mosquito-Borne Viral Infections

• Chikungunya virus presents with similar fever, rash, and arthralgia but typically causes more severe and prolonged joint pain that can persist for months 1
• Zika virus manifests with fever, rash, arthralgia, and conjunctivitis—the conjunctivitis is a distinguishing feature less common in dengue 1
• Both Zika and dengue require NAAT testing on serum collected ≤7 days after symptom onset for definitive diagnosis 2

Other Vector-Borne Diseases

• Malaria must be excluded in any febrile traveler from endemic areas, particularly given its life-threatening potential and specific treatment requirements 1
• Leptospirosis can mimic dengue with fever, myalgia, and headache but often includes conjunctival suffusion, renal involvement, and exposure to contaminated water 1
• Rickettsiosis (including scrub typhus and spotted fever) presents with fever, headache, and rash but typically includes an eschar at the bite site 1

Viral Exanthems

• Measles presents with fever, rash, and conjunctivitis but includes characteristic Koplik spots and a different rash distribution pattern 1
• Rubella causes fever and rash but is typically milder with prominent lymphadenopathy, particularly post-auricular and suboccipital nodes 1
• Parvovirus B19 can cause fever and rash but characteristically produces a "slapped cheek" appearance in children and reticular rash in adults 1

Other Viral Infections

• Hepatitis A should be considered when fever is accompanied by jaundice, right upper quadrant pain, and elevated transaminases 1
• Adenovirus and enterovirus infections can cause undifferentiated febrile illness with rash but typically include respiratory or gastrointestinal symptoms 1

Bacterial Infections

• Group A streptococcal infections (including scarlet fever) present with fever and rash but include pharyngitis, strawberry tongue, and a sandpaper-textured rash 1

Critical Distinguishing Features of Dengue

The CDC defines dengue as fever with one or more of the following: nausea, vomiting, rash, headache, retro-orbital pain, myalgia, arthralgia, positive tourniquet test, leukopenia, or dengue warning signs 1, 2

Key distinguishing features include:

• Retro-orbital pain is highly characteristic of dengue and less common in other febrile illnesses 2
• Leukopenia with thrombocytopenia and rising hematocrit suggests dengue over bacterial infections 2
• Positive tourniquet test indicates capillary fragility specific to dengue 2

Diagnostic Approach Based on Timing

Early Presentation (≤7 days after symptom onset)

• Order dengue PCR/NAAT on serum as the preferred diagnostic method 2
• Simultaneously test for Zika virus NAAT if there is epidemiologic risk for both infections 2
• NS1 antigen detection serves as an excellent alternative, detectable from day 1 to day 10 after symptom onset 2

Late Presentation (>7 days after symptom onset)

• Order IgM capture ELISA for both dengue and Zika virus 1, 2
• A negative NAAT result does not exclude infection due to declining viremia over time 1

Special Considerations

Pregnant Women

Pregnant women must be tested by NAAT for both dengue and Zika viruses, regardless of outbreak patterns, due to risk of maternal death, hemorrhage, preeclampsia, eclampsia, vertical transmission, fetal loss, microcephaly, and serious birth defects. 1, 2

Travel and Epidemiologic Context

• Consider the patient's travel history to dengue-endemic areas (tropics and subtropics where Aedes aegypti mosquitoes are present) 1
• During a dengue outbreak, jurisdictions may elect to forego Zika virus testing in nonpregnant persons with suspected dengue 1, 2
• The incubation period for dengue ranges from 3-14 days, with most cases developing symptoms 4-8 days after infection 2

Common Pitfalls to Avoid

• Do not assume a single negative test rules out dengue—IgM antibodies may not be detectable in specimens collected before development of antibodies 1
• Cross-reactivity with other flaviviruses (yellow fever, Japanese encephalitis, tick-borne encephalitis) can confound serologic testing—document vaccination history 3, 4
• Never use aspirin or NSAIDs when dengue cannot be excluded due to increased bleeding risk 3
• Recent research emphasizes that meningococcemia, malaria, and systemic lupus erythematosus are particularly important differentials that require urgent recognition to prevent mortality 5