Viral Arthropathy and the Zika Virus

In light of the ongoing Zika virus outbreak in the Americas, recognition of the clinical manifestations of infection—including acute onset of low-grade fever with maculopapular rash, arthralgia, and conjunctivitis—can aid in diagnosis.

Arthralgia and arthritis are relatively common occurrences with viral infections. Joint pain is reported in infections with hepatitis A virus (HAV), hepatitis B virus (HBV), alphavirus, dengue virus, Epstein-Barr virus, and others. In HAV infection, arthralgia and rash occur in 10% to 14% of patients, but arthritis is extremely rare.1 From 10% to 25% of patients with HBV infection develop joint symptoms, often with rash and symmetrical arthritis.2 Chronic HBV infection may be associated with more persistent arthritis. More recent reports concerning the global spread of the Zika virus has caused the World Health Organization to declare a global emergency.3

Interim guidelines have been developed for the evaluation and testing of infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy and published in the US Centers for Disease Control and Prevention publication Morbidity and Mortality Weekly Report.4  The European Centre for Disease Prevention and Control have advised that pregnant women consider postponing travel to any area where Zika virus transmission is ongoing, given the association between congenital microcephaly and the Zika virus outbreak in Brazil.5

Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes. Clinical manifestations of Zika virus infection occur in approximately 20% of patients and include acute onset of low-grade fever with maculopapular rash, arthralgia (notably of the small joints of the hands and feet), or nonpurulent conjunctivitis.6 Other commonly reported clinical manifestations include myalgia, headache, retro-orbital pain, and asthenia. Of concern is the association between Zika virus infection and congenital microcephaly and fetal losses among women infected during pregnancy.4   Emerging research has also shown that Zika virus may be transmitted by sexual intercourse.7 

Zika virus infection should be suspected in individuals with relevant history and the characteristic clinical symptoms. The diagnosis of Zika virus infection is definitively established via reverse-transcription polymerase chain reaction (RT-PCR) for Zika viral RNA or Zika virus serology.4 RT-PCR is positive only for a brief window (3 to 7 days) when the infected person has active viremia.  RT-PCR testing for dengue virus and chikungunya virus should also be pursued. Four or more days after the onset of symptoms, the diagnosis may be established by Zika virus serologic testing (Zika virus IgM and neutralizing antibody titers that are ≥4-fold higher than dengue virus neutralizing antibody titers in serum).

There is no specific treatment for Zika virus infection. Management consists of rest and symptomatic treatment including drinking fluids to prevent dehydration and administration of acetaminophen to relieve fever and pain.8 Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) should be avoided until dengue infection has been ruled out to reduce the risk of hemorrhage.

Summary and Clinical Applicability

Currently, there is an ongoing Zika virus outbreak in the Americas.  Rheumatologic manifestations of Zika virus infection include arthralgia, most notably in the small joints of the hands and feet, accompanied by low-grade fever, rash, or nonpurulent conjunctivitis. Zika virus infection has also been associated with congenital microcephaly, fetal loss, and Guillain-Barré syndrome. The diagnosis of Zika virus infection is established via serum RT-PCR testing or serology. There is no specific treatment for Zika virus infection, and there is currently no vaccine for prevention. Management of Zika virus infection consists of symptomatic treatment and fetal surveillance in pregnant women.


1.       Inman RD, Hodge M, Johnston ME, et al. Arthritis, vasculitis, and cryoglobulinemia associated with relapsing hepatitis A virus infection. Ann Intern Med. 1986;105:700-703.

2.       Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004; 350:1118-1129.

3.       World Health Organization Media Centre. WHO Director-General summarizes the outcome of the Emergency Committee regarding clusters of microcephaly and Guillain-Barré syndrome. February 1, 2016. Accessed February 3, 2016.

4.       Staples J, Dziuban E, Fischer M, et al. Interim guidelines for the evaluation and testing of infants with possible congenital Zika virus infection—United States, 2016. Morb Mortal Wkly Rep. 2016;65(3):1-5. doi:10.15585/mmwr.mm6503e3er.

5.       Centers for Disease Control and Prevention. CDC Newsroom: CDC adds countries to interim travel guidance related to Zika virus. January 22, 2016. Accessed February 3, 2016.

6.       Fauci AS, Morens DM. Zika virus in the Americas—yet another arbovirus threat. N Engl J Med. 2016; Jan 13. [Epub ahead of print]

7.       CDC Emerging Infectious Diseases, Vol 21 No 2.

8.   Centers for Disease Control and Prevention. Zika Virus: symptoms, diagnosis, & treatment. Updated January 29, 2016. Accessed January 13, 2016.