INTRODUCTION —
Arthritis and arthralgias are commonly associated with viral infections (table 1) [1-3].
This topic will provide an overview of the causes, the clinical presentation, and a general approach to evaluation and management of these disorders. The evaluation of polyarticular pain in adults is discussed separately. (See "Evaluation of the adult with polyarticular pain".)
CAUSES —
Viruses can initiate joint and other rheumatologic symptoms by a variety of mechanisms, including direct invasion of the joint cells or tissues, immune complex formation, and immune system activation and dysregulation. These mechanisms depend upon host factors, including age, sex, genetics, infectious history, and the immune response [4-8].
Many viruses can cause arthralgias and arthritis (table 1), although the relative prevalence of specific viruses has evolved. As an example, chronic persistent viruses such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV) are becoming less prominent causes of viral arthritis due to vaccinations, pre-exposure prophylaxis, and advances in antiviral therapies. However, other viral infections such as Zika, chikungunya, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become increasingly important [9].
Parvovirus
●Children – Arthritis or arthralgias are relatively uncommon in children [10]. In children, parvovirus B19 is best known for causing the common childhood illness erythema infectiosum. In children (and less commonly, adults), parvovirus B19 infection can also present as a nonspecific febrile illness with a systemic autoimmune rheumatic disease-like syndrome including arthralgia and arthritis [11,12].
●Adults – Parvovirus B19 should be considered in any adult presenting with recent-onset polyarthralgias or polyarthritis.
Arthritis or arthralgias occur in over half of infected adults [10]. In adults, arthralgias or arthritis occur during the acute phase of infection. Arthralgia is more frequent than arthritis; both are more common in females than in males.
Like rheumatoid arthritis, parvovirus B19 affects small joints (including the interphalangeal joints and wrists) in an additive fashion and is associated with prominent morning stiffness. A variety of autoantibodies may be transiently positive during infection including antinuclear antibodies, rheumatoid factor, anti-double stranded deoxyribonucleic acid (DNA) and antiphospholipid antibodies. Their presence may lead the clinician to overlook the possibility of an underlying viral infection.
The joint symptoms may persist for weeks to months prior to resolution, and recurrent arthritis has been reported [13].
Parvovirus B19 may cause a viral arthritis through direct infection of the joint and immune complex formation [13].
Nonarticular manifestations of parvoviral infection are discussed in more detail elsewhere. (See "Clinical manifestations and diagnosis of parvovirus B19 infection".)
Alphaviruses (including chikungunya) — Arthritis is a common feature of many alphavirus infections.
Alphaviruses are one of the main genera of arboviruses (transmitted via arthropod) that cause arthritis. Starting in the early 2000s, there has been an epidemic shift of arboviral infections (especially chikungunya) from the tropics to the Western Hemisphere, prompting rheumatologists and other practitioners to need to consider these infectious etiologies in returning travelers with joint pain. Alphavirus infections may cause joint symptoms mainly through an immune complex reaction induced by virus persisting in synovial macrophages [14].
Alphaviruses are single-stranded, positive-sense ribonucleic acid (RNA) viruses in the family Togaviridae and are often divided into "Old World" and "New World." "Old World" alphaviruses are typically associated with arthritis, while "New World" are associated with encephalitis [15].
There are seven alphaviruses associated with viral arthritis:
●Chikungunya virus – Chikungunya was previously found mainly in South and East Asia, Africa, and the Western Pacific, with recurrent epidemics with as many as 40,000 involved in Thailand in 1962 [16-18]. It has subsequently become a much more global disease with increasing world travel and global warming, with increasing arthritic symptoms including large outbreaks in Italy, India, and Indian Ocean islands as well as reports from islands in the Caribbean since 2013 [19]; subsequently, local transmission was confirmed in many countries and territories in the Caribbean region and in North, Central, and South America [20-22]. Chikungunya fever and the musculoskeletal manifestations of the infection are described in detail separately, as are approaches to the treatment of affected patients and the prevention of infection. (See "Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis" and "Chikungunya fever: Treatment and prevention".)
●Ross River virus and Barmah Forest virus – Ross River virus affects as many as 8000 Australians annually, and the Barmah Forest virus, also found in Australia and Pacific islands, causes approximately 500 to 1500 symptomatic infections per year. These infections are described in more detail separately. (See "Ross River virus infection" and "Potential health hazards in travelers to Australia, New Zealand, and the southwestern Pacific (Oceania)", section on 'Arboviral infections'.)
●Sindbis virus – Sindbis virus was first isolated in Egypt and is linked to Pogosta disease (Finland), Ockelbo disease (Sweden) and Karelian fever (Russia), manifesting with arthritis and rash [17,23].
●Mayaro virus – The Mayaro virus, constituting another group, is found mainly in South America and occurs in small sporadic epidemics, causing arthritis and fever [17,24].
●O'nyong'nyong – O'nyong'nyong is found in Central and East Africa with occasionally small epidemics; however, more than two million people were affected in an epidemic from 1959 to 1962 [17,25]. The clinical presentation is similar to that of chikungunya, with polyarthritis, fever, and rash.
●Igbo-Ora virus – Igbo-Ora, considered as a separate group, is a virus related to O'nyong'nyong and found mainly in Central Africa, with an outbreak in 1988 [17]. Infection is typically associated with a triad of fever, arthritis, and rash [16].
A unique and characteristic feature of these alphaviruses is that they essentially always cause arthritis [26]. Most of these viruses also cause fever, rash, and myalgias. The rash occurs several days after the onset of joint symptoms and is short-lived, involving the face, trunk, and flexor surface of the extremities. Mild lymphadenopathy, mild leukopenia, and lymphocytosis may be present.
The onset in chikungunya and o'nyong'nyong infections is abrupt with fever and joint symptoms and can be severe in nature [17,27,28]. The other alphaviruses are associated with a more gradual onset of fever and nonspecific constitutional symptoms prior to joint involvement [16].
In most patients, the arthritis progressively resolves over an average of a three- to six-month period. However, the Ross River virus and chikungunya may lead to persistent arthritis [29-31], with chikungunya arthritis persisting beyond six months in up to half of those infected. A much smaller proportion develop a chronic inflammatory arthritis with clinical features resembling rheumatoid arthritis. (See "Chikungunya fever: Treatment and prevention", section on 'Prognosis'.)
While alphaviruses like chikungunya and to some degree Ross River have been more heavily studied, most remain endemic to tropical areas and are not as well researched.
Flavivirus
●Zika virus – Clinical manifestations of Zika virus infection include fever, rash, headache, arthralgia, myalgia, and conjunctivitis, although asymptomatic infection is common. Among those with symptoms, arthralgia is characteristic, particularly of the small joints of the hands and feet, but true arthritis has not been reported [32]. Arthralgia, along with the extraarticular symptoms, usually resolves within two to seven days. (See "Zika virus infection: An overview".)
●Dengue virus – The classic findings of dengue virus infection are an acute febrile illness with headaches and marked muscle and joint pain, leading to the moniker "break-bone fever" [33]. Arthralgias occur in 60 to 80 percent of patients. Leukopenia and thrombocytopenia may be present, and liver enzymes may be elevated [34]. Most cases are mild, but a small percentage of patients have potentially lethal forms called dengue hemorrhagic fever and dengue shock syndrome [35]. (See "Dengue virus infection: Clinical manifestations and diagnosis".)
Hepatitis viruses
Hepatitis A virus — True arthritis, rather than arthralgias alone, is extremely rare in patients with hepatitis A virus (HAV) infection.
Arthralgias and rash occur in 10 to 14 percent of patients infected with hepatitis A, most often during the prodromal period. Patients with joint manifestations usually present with knee and ankle arthralgias and an accompanying rash. The arthritis is self-limited and does not become chronic. (See "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Extrahepatic manifestations' and "Overview of hepatitis A virus infection in children", section on 'Clinical manifestations'.)
Arthritis has been described in case reports primarily in patients with vasculitis who had a chronic relapsing form of hepatitis A and also high titer of polyclonal immunoglobulin G (IgG)- and IgM-circulating cryoglobulins (type III cryoglobulinemia) [36].
Overviews of HAV infection are presented separately. (See "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis" and "Overview of hepatitis A virus infection in children".)
Hepatitis B virus — Arthritis is more commonly associated with acute, rather than chronic, hepatitis B virus (HBV) infection.
●Acute HBV infection – Ten to 25 percent of patients with acute HBV develop arthritis, typically during the prodromal stage of the disease, prior to the onset of jaundice [37].
The arthritis may mimic rheumatoid arthritis, presenting with an additive, symmetric, small joint arthritis associated with morning stiffness and rheumatoid factor positivity [38]. However, the arthritis can also be migratory and may affect the large joints [37,39,40].
Arthritis most often occurs in young adults, more often in females than in males. An urticarial or maculopapular eruption primarily involving the lower extremities commonly appears at the same time as the arthritis [37,40].
Arthritis persists for days to weeks and commonly resolves with the onset of jaundice [37,40]. It is always self-limited and does not lead to chronic arthritis or erosive joint damage [41,42].
●Chronic HBV infection – Arthralgias/arthritis are uncommon in patients with chronic HBV infection. When present, they are generally accompanied by myalgias.
When arthritis does occur, it generally appears in association with HBV-associated polyarteritis nodosa, a diagnosis that has become increasingly uncommon. Other manifestations of immune complex-mediated disease may be present, such as glomerulonephritis [43] and essential mixed cryoglobulinemia [44]. Such manifestations have become much less common with the availability of more aggressive and targeted treatment of the infection [39]. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults", section on 'Clinical features'.)
The clinical manifestations, diagnosis, and management of HBV infection are described in detail separately. (See "Hepatitis B virus: Clinical manifestations and natural history" and "Hepatitis B virus: Screening and diagnosis in adults".)
Hepatitis C virus — Arthralgia and myalgia have frequently been reported in patients with hepatitis C virus (HCV) infection, mostly in the context of mixed cryoglobulinemic vasculitis. Frank arthritis is unusual; when it does occur, there is no evidence of joint destruction.
●Acute HCV infection – Arthralgias have been reported in 25 percent of patients with acute HCV infection [45]. Arthritis is rare.
●Chronic HCV infection – Chronic HCV infection is associated with a broad spectrum of extrahepatic manifestations; however, arthritis is uncommon. It should be noted that over half of patients with chronic HCV will have detectable circulating cryoglobulins, but fewer than 5 percent develop symptoms related to mixed cryoglobulinemia (eg, arthritis, purpura, polyneuropathy, glomerulonephritis). Tests for rheumatoid factor, antinuclear antibodies, and anti-SSA antibodies are frequently positive but are not associated with a rheumatic disease.
Direct-acting antivirals have made HCV-associated mixed cryoglobulinemia much less common and have become the treatment of choice for patients presenting with extrahepatic manifestations [46,47].
The clinical manifestations, diagnosis, and management of the mixed essential cryoglobulinemic vasculitis and chronic hepatitis C are discussed in detail separately. (See "Mixed cryoglobulinemia syndrome: Clinical manifestations and diagnosis" and "Mixed cryoglobulinemia syndrome: Treatment and prognosis".)
Rubella and rubella vaccine virus — Rubella and rubella virus vaccine are associated with a high incidence of arthritis.
●Rubella virus – The onset of joint symptoms due to rubella virus is typically abrupt, occurring in most patients within a one-week period before and after the characteristic rash [48,49].
The pattern of joint involvement may be symmetric, migratory, or additive, with resolution of most joint symptoms within two weeks [49-51]. The small joints of the hands, wrists, and knees are most commonly involved. Arthralgias are much more common than arthritis; however, there is often considerable pain and swelling in the soft tissues surrounding the joint as well as synovial tendon sheath involvement, occasionally leading to tenosynovitis and carpal tunnel syndrome [49-51].
In one report, rates were as high as 30 percent of females and 6 percent of males with rubella infection [48]. Joint symptoms may rarely persist as long as a year. However, chronic joint damage does not occur [50,51]. Recurrence of joint symptoms is uncommon.
Rubella virus infection and its complications are described in detail separately. (See "Rubella".)
●Rubella virus vaccine
•Children – Transient arthralgia may develop approximately 7 to 21 days after vaccination with rubella virus vaccine [49,52]. Arthralgias, usually of small peripheral joints, have been reported in 0.5 percent of young children. Recurrence occurs in approximately 1.3 percent of patients with arthralgias [53].
•Adults – Arthralgias occur in 25 percent of adults and postpubertal adolescents following rubella vaccination, and 10 percent develop arthritis, which is also transient [54]. One study showed that the risk of arthritis following rubella vaccination may be higher in females who have very low prevaccine levels of neutralizing antibodies [55].
Both rubella and rubella virus vaccine may directly infect the synovium, although isolation of virus from the joint is uncommon [49,56-60].
The adverse effects of rubella vaccination are described in detail separately. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'Adverse effects' and "Measles, mumps, and rubella immunization in adults".)
Human immunodeficiency virus infection — HIV infection has been associated with several rheumatic disease syndromes, although advances in screening and treatment is making it less common as a cause of rheumatic disease [61-64]. A combination of immunodeficiency, immune hyperactivity, dysregulated production or activity of cytokines, and molecular mimicry may contribute to the rheumatic manifestations of HIV infection [61].
Epidemiologically, antiretroviral therapy has made the syndromes discussed below much less common. However, HIV is still underdiagnosed and undertreated, making it important to consider these syndromes in the appropriate clinical setting.
HIV-related joint conditions — Several conditions affecting the joints appear to be HIV-specific:
●Arthralgia/arthritis associated with acute infection – Patients newly infected with HIV may experience an infectious mononucleosis-like syndrome that includes arthralgias and myalgias, among other findings [63,65]. Joint pain most often involves the knees, shoulders, and elbows. Symmetric "viral polyarthritis" has also been reported [63]. These symptoms are self-limited, usually lasting for two weeks.
●Painful articular syndrome – Patients with chronic HIV infection may develop the painful articular syndrome, which is a self-limited disorder lasting for less than 24 hours in patients that causes severe arthralgias but not arthritis [62]. The pain is excruciating and debilitating. It is associated with later stages of infection and is reported in up to 10 percent of African patients with HIV and some other groups, but not in all case series [63]. Bone and joint pain is noted, especially in the lower extremities in an asymmetric pattern, which is out of proportion to clinical findings, often requiring hospitalization and even opioids to manage pain. The etiology is not known and treatment is symptomatic.
●HIV-associated arthritis – Patients at any stage of HIV illness can develop HIV-associated arthritis, which is a self-limited nondestructive arthritis, usually lasting less than six weeks [66,67]. The prevalence ranges from 0.4 to 13.8 percent [68] and has a male preponderance. Joints of the lower extremity are usually involved in an asymmetric, oligoarticular pattern. Synovial fluid is inflammatory. Rarely, a more prolonged course with joint destruction has been noted [62].
HIV impact on non-HIV rheumatic disorders — With the widespread use of combination antiretroviral therapy, arthritis in a patient with HIV is more likely due to a concomitant rheumatic disease than HIV. Patients with both HIV and a rheumatic disease can be challenging to treat.
●Reactive arthritis – Reactive arthritis (the primary form of spondyloarthritis seen in patients with HIV) was first described in 1987, in 13 patients with acquired immunodeficiency syndrome (AIDS) and severe oligoarticular arthritis with features of reactive arthritis [69]. The prevalence in people with HIV ranges from 1.7 to 11.2 percent [70]. Human leukocyte antigen B27 (HLA-B27) is positive in roughly 70 percent of White patients with HIV-associated reactive arthritis [71]. A similar association is not seen in Black African patients. This reactive arthritis is thought to be associated with late stages of immunosuppression (eg, uncontrolled HIV).
The classic triad of arthritis, urethritis, and conjunctivitis is not common; rather, an incomplete form of reactive arthritis usually occurs [72]. Axial involvement and uveitis are uncommon in HIV-associated spondyloarthritis [62]. Mucocutaneous disease, including keratoderma blennorrhagicum, circinate balanitis, and psoriaform skin disease is often present, especially in patients with HIV and a positive HLA-B27, who tend to have worse disease outcomes [73].
In sub-Saharan Africa where HIV is highly prevalent, HLA-B27-associated spondyloarthritis is rare. Other genetic factors such as HLA-B*5703 have been noted in patients with HIV and spondyloarthritis in Zambia [74]. The clinical manifestations of reactive arthritis in patients with HIV are similar to those in other populations. (See "Reactive arthritis".)
Reactive arthritis in HIV is clinically distinguished from HIV-associated arthritis in its chronicity and relapsing nature, by the presence of enthesopathy and mucocutaneous manifestations, and by HLA-B27 positivity [75], though multiple joint involvement has been reported in cases of septic arthritis caused by Salmonella species. (See "Septic arthritis in adults".)
●Psoriatic arthritis – The prevalence of psoriatic arthritis (PsA) in patients with HIV is 1 to 2 percent, similar to that in patients without HIV; the severity is often worse in HIV patients, especially those not being treated with antiretroviral therapy [76]. The most commonly and most severely affected joints are generally those of the feet and ankles. As with reactive arthritis, frank synovitis is unusual and enthesitis may be a disabling clinical feature. Axial involvement may occur and be associated with radiographic changes of sacroiliitis [61]. Peripheral joint radiographs may reveal "pencil in cup" deformities and osteolysis similar to those seen with classic PsA, and these may be present in the absence of frank psoriatic skin involvement (ie, PsA sine psoriasis). (See "Treatment of psoriatic arthritis".)
Two forms of PsA have been reported in patients with HIV. The first is a sustained and aggressive type of arthritis leading to joint erosion, and the second is a mild and intermittent pattern of joint involvement. There is a strong association of HLA-B27 with pustular psoriasis and PsA in HIV patients [76].
●Immune reconstitution inflammatory syndromes – New autoimmune or inflammatory disease or flares of preexisting disease, such as sarcoidosis or rheumatoid arthritis-like illnesses, have been reported in association with reconstitution of T-cell-mediated immunity [77]. Adult-onset Still's disease has also been reported, as have a number of autoimmune but nonrheumatologic disorders. The pathogenesis and features of the immune reconstitution inflammatory syndromes (IRIS) seen in some patients with restitution of immune function are described in detail separately. (See "Overview of immune reconstitution inflammatory syndromes".)
Other viral etiologies
●Mumps virus – Arthritis is uncommon in patients with mumps, with fewer than 100 cases reported in the literature. Mumps is characterized by parotitis, which is usually bilateral and follows a short prodromal phase with nonspecific constitutional symptoms. However, some symptomatic patients do not have parotitis [78,79].
If present, the arthritis typically occurs after the onset of parotitis. A migratory polyarthritis involving both large and small joints is the most common presentation, but polyarthralgias or monoarthritis can also occur [78,79]. Low-grade fever typically accompanies the joint symptoms, which generally resolve over a period of weeks. No long-term joint damage has been reported. The mechanism by which mumps virus gives rise to joint symptoms is not known. The general features of mumps are discussed elsewhere. (See "Mumps".)
●Adenovirus infection – Adenoviruses comprise a large family of immunotypes with a wide range of clinical illnesses. Only a small number of cases of adenovirus-associated arthritis have been reported [80]. Affected patients typically present with mild fever, nonspecific constitutional symptoms, arthralgias, arthritis mainly of the knees, and rash. The disease is typically self-limited but may persist over a year in some cases [80]. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infections" and "Diagnosis, treatment, and prevention of adenovirus infection".)
●Herpesvirus infections – A number of arthritis syndromes may be associated with the herpesvirus family. Epstein-Barr virus (EBV) is the most common cause of arthralgias and arthritis of this group, but the other members of this family, including varicella-zoster virus, herpes simplex virus, and cytomegalovirus, may infrequently also cause joint symptoms.
•Epstein-Barr virus – Approximately 90 percent of patients newly infected with EBV, the primary agent of infectious mononucleosis, are asymptomatic. Of the 10 percent with symptoms, the majority have arthralgias; true arthritis is less common [81,82].
Arthralgias are the most common joint findings, with occasional large-joint swelling, and arthrocentesis may reveal an inflammatory joint fluid [78,81]. The joint complaints usually occur in the first weeks of the infection and can be acute in nature. Overall, the joint signs and symptoms are self-limited [81,83]. Epstein-Barr viral infections have been implicated in complicating treatment of juvenile idiopathic arthritis, especially for patients on biologic response modifiers [82]. Awareness of a past or present EBV infection may help in determining treatment options [82].
The clinical manifestations, diagnosis, and management of EBV infection are described in detail separately. (See "Virology of Epstein-Barr virus" and "Clinical manifestations and treatment of Epstein-Barr virus infection" and "Infectious mononucleosis".)
•Varicella – Arthritis associated with chickenpox (varicella) is a rare but well-described phenomenon that occurs within several days of the onset of the rash [84,85]. Monoarticular knee involvement is most common, with swelling, pain, and limitation of motion. However, the pain is thought to be due to viral involvement of the nerve root, rather than the joint itself. (See "Clinical features of varicella-zoster virus infection: Chickenpox".)
•Herpes simplex virus – Arthritis associated with herpes simplex virus has been reported on a few occasions, all associated with a generalized herpes simplex virus type 1 infection [86,87]. In most cases, the disease is self-limited, resolving in 10 days to three months. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection".)
•Cytomegalovirus – Cytomegalovirus arthritis is rare, but severe cytomegalovirus polyarthritis has been described in several immunocompromised bone marrow transplant recipients [78,86]. These patients had painful, warm, swollen knees, and joint aspiration yielded a noninflammatory synovial fluid; joint symptoms persisted for several months. Acute arthralgias have also been reported in kidney transplantation patients with cytomegaloviral infections [78,88,89]. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Approach to the diagnosis of cytomegalovirus infection" and "Overview of cytomegalovirus (CMV) infections in children".)
●Coronavirus – Coronavirus is not usually associated with rheumatologic symptoms; however, SARS-CoV-2 infection has rarely been associated with post-reactive arthritis that responds to nonsteroidal antiinflammatory drugs (NSAIDs) [90]. Multisystem inflammatory syndrome in children (MIS-C) is associated with arthralgia [91], and, very rarely, a similar syndrome may be seen in adults. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis" and "COVID-19: Care of adult patients with systemic rheumatic disease", section on 'Multisystem inflammatory syndrome in adults'.)
●Enterovirus – Arthritis occurs in only 0.1 percent of patients infected with enterovirus [1-3]. It occurs simultaneously with other symptoms of acute viral infection, including fever, sore throat, pleuritic pain, myocarditis, and rash. Both large and small joints may be involved. Routine laboratory findings are nonspecific and include leukocytosis, elevated erythrocyte sedimentation rate, and synovial fluid white blood cell counts ranging from 2000 to >10,000/mm3.
The incubation period for viral infection is short (ie, three to five days) and is followed by the abrupt onset of fever, headache, and other nonspecific constitutional signs and symptoms. There may be associated maculopapular rash, pharyngitis, conjunctivitis, myalgias, nausea, vomiting, diarrhea, and abdominal pain. Symptoms are generally short-lived (ie, two to four days), although they may recur [92]. Enterovirus may cause arthritis through direct infection of the joint [1]. (See "Enterovirus and parechovirus infections: Epidemiology and pathogenesis" and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention".)
COMMON CLINICAL FEATURES —
There is no single presentation that is typical of viral arthritis; however, in general, common features include:
●Sudden-onset polyarthritis
●Self-limited duration
●Lack of erosive joint damage
●Travel history to endemic location
●Concomitant fever, constitutional symptoms, or viral exanthem.
Arthritis may precede other signs of viral infection (eg, before icterus in hepatitis B virus [HBV] infection).
Specific features of the different viruses that cause arthritis are discussed elsewhere. (See 'Causes' above.)
EVALUATION AND DIAGNOSIS
Acute arthritis
Establish the presence of arthritis — Arthralgia (ie, the subjective complaint of joint pain) is a common feature of many viral infections. However, only a subset of viruses cause true arthritis (objective evidence of synovial hypertrophy and joint inflammation).
Symptomatology alone is not adequate to establish a diagnosis of arthritis. Diagnosing polyarthritis requires examination of the upper and lower extremity joints to look for evidence of synovitis.
If a full musculoskeletal examination is not possible, screening patients for diminished grip strength may help identify patients with early polyarthritis [93]. Subclinical joint inflammation and tenosynovitis in hand joints cause diminished grip strength, which may be easier to detect than true synovitis.
The joint examination in patients with suspected arthritis is discussed in more detail elsewhere. (See "Evaluation of the adult with polyarticular pain", section on 'Joint examination'.)
When to suspect viral etiology — We suspect viral arthritis in a patient presenting with an acute (eg, less than four weeks) polyarthritis associated with recent travel, sick contacts, or clinical evidence of a viral infection (eg, rash and/or fever) (algorithm 1).
Acute monoarthritis is unlikely to be caused by a viral infection. In children, varicella can rarely cause acute monoarthritis. Patients presenting with acute monoarthritis should also be evaluated for nonviral etiologies, such as crystalline or septic arthritis. (See "Gout: Clinical manifestations and diagnosis" and "Calcium pyrophosphate crystal deposition (CPPD) disease: Clinical manifestations and diagnosis" and "Septic arthritis in adults".)
Among patients with suspected viral arthritis, certain features may be suggestive of particular viral etiologies (see 'Causes' above):
●Arthritis – True arthritis can be associated with acute and chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV), parvovirus B19, rubella, alphaviruses (eg, chikungunya), flaviviruses (eg, Zika), and HIV infection.
●Extra-articular physical findings – Characteristic rashes may be associated with rubella, parvovirus B19, and varicella. Parotid enlargement may be found with mumps. Palpable purpura or other evidence of vasculitis may be associated with viral hepatitis.
●Laboratory tests – Elevated transaminase levels and hyperbilirubinemia may occur in multiple viral infections, including viral hepatitis. Anemia with a low reticulocyte count may be caused by parvovirus B19 infection. Viral hepatitis and parvovirus B19 frequently cause positive auto-antibodies (eg, antinuclear antibodies, rheumatoid factor, etc).
●Travel – Alphaviruses and flaviviruses have geographic distributions specific to each species. (See 'Other viral etiologies' above.)
●Pattern of joint involvement – Migratory arthritis may be indicative of hepatitis B virus or rubella, although an additive pattern is more common. Acute monoarthritis may rarely be found with varicella infection or chronic hepatitis B.
●Comorbidities – Immunocompromised patients, including those with HIV, can develop arthritis related to cytomegalovirus. HIV is also directly associated with multiple joint manifestations. (See 'HIV-related joint conditions' above.)
●Vaccination status – Many vaccinations are associated with transient arthralgias. Rubella vaccine is associated with a high incidence of arthritis. Vaccination against hepatitis B, rubella, or SARS CoV-2 makes these etiologies less likely to cause a viral arthritis.
Laboratory findings (including synovial fluid analysis) are generally of little value in differentiating viral arthritis from other musculoskeletal conditions, unless characteristic findings of another disorder are present.
Limited role for diagnostic testing — We do not suggest a standard panel of tests for all patients presenting with acute viral arthritis. Acute viral arthritis is most commonly caused by a self-limited viral infection and by itself is not an indication for extensive testing. The diagnosis of viral arthritis is made indirectly when the diagnosis of the systemic infection is made (see below). The approach to diagnosing these infections is discussed in dedicated topic reviews.
●Indications for additional testing – Specific diagnostic testing may be indicated when the arthritis is part of a viral syndrome that raises suspicion for a particular etiology that has management or public health implications. This includes acute or chronic HIV infection, viral hepatitis, and rubella, mumps, or varicella virus infections. Additionally, it is reasonable to screen adult patients at least once for hepatitis B, hepatitis C, and HIV, and more frequently if risk factors are present; this is discussed in detail elsewhere. (See "Hepatitis B virus: Screening and diagnosis in adults" and "Screening and diagnosis of chronic hepatitis C virus infection" and "Screening and diagnostic testing for HIV infection in adults".)
●Caveats for serologic and antibody testing – Diagnostic tests specific for some viruses exist. For other viruses, testing includes assessment of IgG and IgM antibodies. IgG antibodies to a number of viruses may be present due to prior exposures unrelated to the current illness. This is a particular problem with parvovirus and enterovirus, which are endemic in many populations. Similar considerations apply to alphaviruses (such as Barmah Forest, Ross River, chikungunya, Mayaro, and Sindbis virus) in regions where these infections are endemic. In such cases, a positive IgM antibody or an increase in IgG titers greater than fourfold between the acute and convalescent period suggest recent infection.
●Limited role for synovial fluid tests – Isolation of a virus directly from synovial fluid or tissue is not a common clinical practice and has not been well validated for clinical use. Similarly, polymerase chain reaction (PCR)-based tests are unreliable for identifying the etiology of viral arthritis. PCR has predominantly been used to identify specific bacteria (but not viruses) in patients with culture-negative periprosthetic joint infection [94]. PCR of synovial fluid and tissue from patients with inflammatory arthritis may identify multiple viruses that have a tropism for inflamed synovial tissue but are not pathogenic [95]. These viruses include cytomegalovirus, parvovirus B19, Epstein-Barr virus (EBV), and herpes simplex virus. A positive synovial specimen PCR in such cases is not necessarily indicative of viral arthritis.
Diagnosis — The diagnosis of acute viral arthritis is made clinically and presumptively, based on clinical presentation in a patient with acute arthritis and concurrent viral infection (see 'When to suspect viral etiology' above). The diagnosis of viral arthritis is clinically supported by resolution of symptoms in a few weeks (algorithm 1). If the arthritis persists, additional evaluation is warranted. (See 'Chronic arthritis' below.)
Chronic arthritis — Viral infection rarely leads to chronic arthritis. Therefore, testing for viruses in most cases of chronic arthritis is unnecessary. Most chronic arthritis is due to rheumatic illness (eg, rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus). (See 'Differential diagnosis' below.)
An important exception is chikungunya-related arthritis, which may mimic more serious and persistent forms of noninfectious arthritis, with almost half of patients still having joint symptoms six months after the start of infection. Chikungunya-related arthritis should be suspected in patients with epidemiology (ie, travel to an endemic area) related to the onset of symptoms. The evaluation and diagnosis of chikungunya is discussed elsewhere. (See "Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
Rubella virus, parvovirus, EBV, and other alphaviruses may rarely induce persistent arthritis, but these forms of chronic arthritis are uncommon [13,58-60,96-98].
DIFFERENTIAL DIAGNOSIS —
Arthritis that persists for longer than six weeks without improvement requires consideration of alternate diagnoses. There are multiple other causes of polyarticular joint pain, particularly rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, and juvenile idiopathic arthritis, all of which may be difficult to distinguish from viral arthritis early in the disease course (table 2). With time, rheumatic diagnoses tend to develop pathognomic features that help confirm the clinical diagnosis (table 3). Immunodeficiencies may also present with arthralgias and arthritis. In some cases, the correct diagnosis may be apparently only in retrospect, after observing the clinical course and response to therapy over several months. The differential diagnosis and evaluation of polyarticular pain and polyarthritis are reviewed in detail separately:
●Evaluation of polyarticular pain (see "Evaluation of the adult with polyarticular pain")
●Diagnosis of rheumatoid arthritis (see "Diagnosis and differential diagnosis of rheumatoid arthritis")
●Diagnosis of systemic lupus erythematosus (see "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis")
●Diagnosis of spondyloarthritis (see "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults")
●Diagnosis of juvenile idiopathic arthritis (see "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis")
●Clinical manifestations of common variable immunodeficiencies (see "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults")
MANAGEMENT —
Most viral arthritides are self-limited, and treatment is generally supportive.
Supportive care — We suggest treatment with analgesic agents (eg, acetaminophen) and nonsteroidal antiinflammatory drugs (NSAIDs) in doses typically used in inflammatory arthritis (table 4), such as rheumatoid arthritis. (See "Initial treatment of rheumatoid arthritis in adults", section on 'NSAIDs'.)
Aspirin should be avoided in children and young adults, given the association between aspirin and Reye syndrome. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)
Physical and occupational therapy can be initiated if required to maintain or improve function.
Limited role of glucocorticoids — In general, we avoid glucocorticoids, which may mask the disease and worsen underlying infection. However, we suggest short courses of glucocorticoids (eg, prednisone up to 15 mg daily followed by a rapid taper over a week) for patients with debilitating symptoms. It should be noted that caution must be used for HIV patients in whom a trial of prednisone for arthritis management is being considered, as many antiretroviral regimens have significant drug interactions with glucocorticoids.
Treatment of the underlying cause — When a specific etiology of viral infection is identified, the decision to initiate antiviral therapy is generally driven by considerations other than the presence of arthritis. Most viral arthritis is caused by viruses that lack specific therapies. Management of the treatable viral causes of arthritis are discussed in detail separately. (See "Hepatitis B virus: Overview of management" and "Overview of the management of chronic hepatitis C virus infection" and "Acute and early HIV infection: Treatment".)
Treatment of the underlying infection should lead to resolution of the viral arthritis after several weeks. However, there are reports of persistent rheumatic syndromes following eradication of an underlying viral infection [99-101]. In these cases, patients are often treated with the same immunosuppressive drugs used for idiopathic rheumatic diseases, although the efficacy of this approach for chronic viral arthritis is unclear. (See "General principles and overview of management of rheumatoid arthritis in adults" and "General principles and overview of management of rheumatoid arthritis in adults", section on 'Pharmacologic therapy'.)
Specific treatment considerations for specific viral infections are discussed elsewhere.
SUMMARY AND RECOMMENDATIONS
●Causes – A wide variety of viral infections can cause arthritis (table 1). Because of changing epidemiology, hepatitis viruses and HIV are less common causes of viral arthritis, whereas other infections, including Zika and chikungunya viruses, are becoming more important. In adults, parvovirus B19 is particularly important to consider, since its presentation may be confused with rheumatoid arthritis. (See 'Causes' above.)
●Clinical features – Common clinical features include sudden onset polyarthritis of self-limited duration with concomitant fever, constitutional symptoms, exanthem, or other extraarticular features of systemic infection. In some cases, arthritis may precede other clinical manifestations. (See 'Common clinical features' above.)
●Evaluation and diagnosis – The likelihood of a viral etiology depends on the time course of symptoms (algorithm 1):
•Acute arthritis – Among patients with acute arthritis (eg, less than four weeks), we suspect a viral etiology in those with polyarthritis after recent travel, potential exposure to viral infections, or extraarticular symptoms. Certain such features may suggest specific viral etiologies (eg, migratory arthritis with hepatitis B infection or rubella). Acute monoarthritis is rarely caused by viral infection and should prompt evaluation for alternative causes.
Because viral arthritis is typically self-limited, extensive testing to establish the viral etiology is generally not indicated. The diagnosis is made presumptively based on the presence of consistent clinical features and supported by resolution within a few weeks. When specific testing for viruses is performed (eg, for public health reasons or to screen for HIV or viral hepatitis), acute arthritis can generally be attributed to the detected infection, particularly if it resolves spontaneously or with treatment of the infection. (See 'Acute arthritis' above.)
•Chronic arthritis – With the exception of chikungunya virus, viral infection rarely leads to a chronic arthritis, so patients who have arthritis that lasts longer than six weeks should be evaluated for other causes (table 2), including rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, and juvenile idiopathic arthritis. (See 'Chronic arthritis' above and 'Differential diagnosis' above.)
The evaluation of chronic polyarthritis is discussed in detail elsewhere. (See "Evaluation of the adult with polyarticular pain".)
●Management – Acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) are generally sufficient for symptomatic treatment (table 4). For patients with debilitating symptoms, we suggest a short course of glucocorticoids (Grade 2C). Glucocorticoids may provide faster relief of symptoms; however, they may exacerbate an underlying infection and we thus reserve them for severe cases. Most viral causes of arthritis have no specific management; for those that do, treatment of the underlying infection is associated with resolution of arthritis. (See 'Management' above.)