Clinical presentations and course
Epstein-Barr virus (EBV)
EBV infections are typically asymptomatic, reflected in the high rates (80%) of people with IgG antibodies directed at EBV.1 However, when acute infections do occur, all will have memorable pharyngitis and 95% will have cervical adenopathy. Arthritis is relatively rare and does not occur in isolation, although widespread myalgias are common. Other herpes viruses, such as cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella zoster virus (VZV) are unusual causes of arthritis.2
Adenovirus and enterovirus
Adenovirus rarely causes arthritis and is usually acquired asymptomatically or manifests as respiratory tract or gastrointestinal infection.2 Similarly, enteroviruses (Coxsackie virus and echoviruses) may have protean manifestations, most typically non-specific febrile illness, aseptic meningitis, pleurodynia or exanthems. They are most unlikely to present with isolated joint manifestations.
Parvovirus B19
Parvovirus B19 infections in children present as a viral exanthema, and in adults as a cause of arthralgia and arthritis. The incubation period is 7–10 days with non-specific flu-like symptoms in the first week followed by arthralgias or arthritis in up to 60% of patients in the second week. Up to 75% of adults will have a rash, although only 20% will have the typical ‘slapped cheek’ appearance.3 The hands, feet and knees are commonly affected, usually symmetrically. Pain, rather than swelling, is the dominant feature. A dramatic decrease or absence of reticulocytes is a hallmark laboratory finding. Rarely, joint symptoms persist for months or years, but the arthritis is non-destructive.
Hepatitis A
In its prodromal phase, hepatitis A infection in adults usually presents with flu-like symptoms. The infection then progresses to the icteric phase, which may include jaundice, bilirubinuria, pruritus and abdominal pain. Arthralgias and rash occur in 10–14% of patients, but arthritis is extremely rare.4
Hepatitis B (HBV)
HBV infection may be asymptomatic, but symptomatic patients will develop constitutional symptoms in the prodromal period. During this period, HBV-infected hosts can develop a sudden-onset, transient polyarthritis (involving the wrists, knees, ankles and small joints of the hands) that may mimic the onset of RA, although typically accompanied by a rash. The arthritis usually subsides at the onset of jaundice.5
Hepatitis C (HCV)
HCV infection is usually asymptomatic but can present with acute hepatitis, nausea and abdominal pain. HCV infection becomes chronic in about 80% of patients and is usually asymptomatic or manifests with mild, non-specific symptoms.6 Polyarthralgias occur in approximately 20% of patients with chronic HCV and an inflammatory oligoarthritis or polyarthritis (mimicking RA but not destructive) occurs in 2–5% of patients. Chronic HCV infection is associated with abnormal immune function, including cryoglobulinemia and positive rheumatoid factor, leading to potential diagnostic confusion. It is important to exclude HCV in RA patients as HCV infection can be exacerbated by immunosuppressive therapy.
Human immunodeficiency virus (HIV)
Early HIV infection may be asymptomatic or present with a variety of non-specific symptoms and signs, including constitutional symptoms, adenopathy, pharyngitis and frequently a rash. Arthralgias and arthritis are present in 5.5% of people with HIV.7 Acute HIV-associated arthritis tends to be self-limiting, lasting less than 6 weeks. It will usually present as oligoarticular or polyarticular, with negative tests for antinuclear antibodies and rheumatoid factor. Established HIV infection is associated with a number of rheumatic syndromes that fall outside the scope of this review.
Ross River virus (RRV) and Barmah Forest virus (BFV)
RRV and BFV are arthritogenic alphaviruses and are transmitted by mosquito vectors with intermediate hosts.8 They are responsible for 5000–8000 Australian cases of polyarthritis annually, with decreasing prevalence from north to south, although changing land practices and climate change are likely to influence this distribution. RRV is most common among adults aged 25–44 years and there is equal sex distribution.9 The incubation period is 2–10 days with a characteristic sudden onset of illness.8 The symptoms are typically non-specific and include polyarthralgia (85–98% of patients), myalgia (60%), rash (50%, typically maculopapular and more common and florid in BFV) and fever (35–50%); half to two-thirds of patients are asymptomatic. Joint symptoms and signs are usually symmetrical and acute in onset, and ankles, fingers, wrists and knees are most commonly affected. Effusions are often present and the distribution can be similar to that seen in polyarticular RA.9 The erythrocyte sedimentation rate (ESR) can be transiently elevated but C-reactive protein is rarely increased. The arthropathy typically resolves within a few weeks to a few months. Almost all patients with symptoms beyond 6 months have other conditions, such as osteoarthritis, autoimmune arthritides and depression, that account for their disease.10
Measles, mumps and rubella
Rubella classically presents with a maculopapular rash on the face that spreads to involve the trunk, hands and feet, sparing the palms and soles, accompanied by significant head and neck lymphadenopathy. Rubella and rubella vaccine are associated with arthritis, which occurs in 30–50% of females and 6% of males.11 The arthritis is similar to that in rheumatic fever and the small joints of the hands, wrists and the knees are most commonly involved. Arthralgia is much more common than frank arthritis, and peri-articular involvement is frequently seen. The arthritis typically starts in the week before and after the onset of rash and usually resolves within 2 weeks. Arthritis with mumps is extremely rare, with small or large joint synovitis within 4 weeks of parotitis. Symptoms can persist for up to several weeks.12 Arthritic presentations of measles virus have not been described.13
A summary of the clinical presentations of viral arthritis is given in Table 1.
Table 1. Clinical presentations of viral arthritis
| Virus | Frequency of arthritis | Typical presenting features | Likelihood of presenting with arthritis | Duration of arthritis | Comments |
|---|
| EBV |
Very low |
- Pharyngitis, cervical lymphadenopathy
- Fevers
|
Very low |
Days |
Often have myalgias with acute infection |
| Herpes viruses |
Very low |
- CMV – infectious mononucleosis
- VZV – chicken pox/shingles
- HSV mucosal infections
|
Very low |
N/A |
Rarely associated with arthritis.
Specific treatments indicated for some non-articular manifestations |
| Adenovirus and enterovirus |
Very low |
- Upper respiratory tract infections, gastrointestinal symptoms, conjunctivitis
|
Very low |
N/A |
|
| Parvovirus B19 |
High |
- Viral exanthem in children
- Arthritis/arthralgia in adults with preceding febrile illness
|
High |
Days but may be prolonged for months |
Diagnosis assisted by concurrent demonstration of IgM and IgG antibodies |
| Hepatitis A |
Low |
- Flu-like illness followed by jaundice
|
Low |
Days |
Arthralgia more common than frank arthritis |
| Hepatitis B |
Moderate |
|
Moderate |
Days/weeks |
Arthritis is abrupt in onset, in RA distribution preceding icteric phase |
| Hepatitis C |
Moderate |
|
Moderate |
Weeks, months in chronically infected patients |
Chronic arthralgia (20%); true arthritis (2–5%) |
| HIV |
Low |
- Acute infectious mononucleosis-like illness at seroconversion in some patients.
|
Low |
|
Arthritis, arthralgia with acute infection.
Increased incidence of several rheumatic diseases in chronic infection |
| RRV |
Very high |
- Arthralgia, myalgia, rash, fever
|
Very high |
Weeks to months |
Diagnosed by demonstration of seroconversion. Can rarely be associated with prolonged arthritis |
| Mumps |
Very low |
- Parotitis and lymphadenopathy
|
Very low |
Weeks |
|
| Rubella |
High |
- Acute maculopapular rash, sparing the palms and soles
|
High |
Weeks |
Can occur with rubella vaccine |
Early inflammatory arthritis
Patients presenting with early inflammatory arthritis, particularly those with RA, have long-term benefits from the early institution of disease-modifying therapy. The suspicion of RA is raised by several clinical features (Table 2). These patients benefit from early specialist referral. The utility of investigating patients with early, undifferentiated arthritis for viral causes has been assessed in a large, early arthritis cohort.14 Where arthritis had persisted for more than 6 weeks, the prevalence of previously unknown arthritogenic viral infection was 0.25% for parvovirus, 0% for HBV and HIV, and 0.37% for HCV. Routine screening was therefore not recommended. In Australia, RRV may also be associated with a more persistent arthritis, but the utility of screening similar patients is unknown. Although suspected of contributing to the triggering of rheumatic disease, there is no evidence that viruses cause autoimmune disease or destructive arthritis.
Table 2. Features suggesting rheumatoid arthritis
- Symptom duration of longer than 6 weeks
- Early morning stiffness for longer than one hour
- Arthritis in three or more regions
- Bilateral compression tenderness of the metatarsophalangeal joints
- Symmetry of areas affected
- Rheumatoid factor positive
- Anti-cyclic citrullinated peptide (anti-CCP) antibody positive
- Bony erosions evident on X-rays of the hands or feet (uncommon in early disease)
- Family history of inflammatory arthritis
|
| Reproduced with permission from Rheumatology Expert Group. Features suggesting rheumatoid arthritis (box 8). In: Therapeutic guidelines: Rheumatology. Version 8. Melbourne: Therapeutic Guidelines Limited; 2010. p.82. |
Establishing the diagnosis
Viral arthritis is typically associated with symptoms of a flu-like illness and systemic signs such as a viral exanthem, fever and lymphadenopathy, and these features should be sought on history and examination. Most presentations are with a polyarthritis; a monoarthritis should prompt investigation for other aetiologies.
The presence or absence of extra-articular features of an autoimmune disease should also be elicited. Confirmation of a recent viral infection requires an appropriate change in paired serology (Table 3)15. Given the high rate of infections in the general population (as with EBV), positive IgG antibodies alone are non-diagnostic. Similarly, IgM antibodies do not always represent recent infection as they can persist for up to 2 years.16 Testing for antinuclear antibodies, rheumatoid factor and anti-citrullinated protein antibodies (ACPA) is useful in evaluating people with typical or persistent presentations of inflammatory arthritis, but are neither sufficiently sensitive nor specific to make diagnoses alone. Viral arthritis can be associated with rheumatoid factor, although this is usually at low titre and transient. There are a number of differentials for a polyarthritis; however a full discussion of these is beyond the scope of this review.
Table 3. Criteria for serological diagnosis of an acute viral infection (requires a change between acute and convalescent serology)15
| Acute serology | Convalescent serology |
|---|
| IgM+ and IgG– |
IgM+ and IgG+ |
| IgM– and IgG– |
IgM+ and IgG+ |
| IgM+ and IgG– |
IgM– and IgG+ |
| Or a 4-fold increase in paired serology tests |
Specific testing for viral arthritis is indicated if treatable diseases are suspected on the basis of the clinical picture (such as HCV or HIV), or when reassurance is important. As both RRV and BFV are notifiable diseases in Australia, a serological diagnosis should be made if the clinical suspicion is high. Routine screening for all potential arthritogenic viruses is not advised.
General treatment
Viral arthritis that has been evident for less than 6 weeks is treated symptomatically. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment. The potential benefits of NSAIDS should be weighed up against their potential risks. It is essential to provide reassurance to the patient that the symptoms are self-limiting and unlikely to develop into a serious condition, such as RA, or cause joint destruction or disability. The use of corticosteroids is to be discouraged unless there are troublesome symptoms and contraindications to NSAIDs, or where a brief course of low dose (<10 mg of prednisone daily) may be reasonable.
When to refer
Specialist referral for acute viral arthritis is rarely needed. It should be considered when arthritis persists beyond 6 weeks, where an early inflammatory arthritis such as RA is suspected or where investigation results are ambiguous or inconsistent with the clinical findings. Patients with suspected HIV, HBV or HCV may also benefit from specialist referral.
Key points
- Viral arthritis is typically self-limiting and requires no specific intervention.
- Arthritis may be a manifestation of an important treatable viral infection, such as hepatitis or HIV.
- Some viruses have a predilection for the joints and result in prolonged symptoms.
- Early systemic inflammatory arthritis can be difficult to differentiate from viral arthritis and should be actively considered in all patients.
Competing interests: None.
Provenance and peer review: Commissioned; externally peer reviewed.