eMedicine Specialties > Rheumatology > Infectious Arthritis

Viral Arthritis

Author: Rabea Ahmed Khouqeer, MD, FRCP(C), Consultant, Department of Medicine, Division of Allergy and Clinical Immunology/Rheumatology, Saad Specialist Hospital, Saudi Arabia
Coauthor(s): Martin Cohen, MD, Adjunct Professor, Department of Medicine, McGill University Health Center
Contributor Information and Disclosures

Updated: Aug 1, 2008

Introduction

Background

Viral arthritis is characterized by inflammation of the joints caused by a viral infection. Identifying and understanding the pathophysiologic mechanisms by which viral arthritis causes acute and chronic arthropathies is crucial to understanding its immunopathogenesis. Alterations of the immune system can lead to acute forms of arthritis, which can be followed by chronic arthralgia or arthritis (ie, overrepresentation of CD8⁺ T lymphocytes in the synovial fluid of individuals with rheumatoid arthritis or Epstein-Barr virus infection).

The number of patients diagnosed with acute viral arthritis is relatively low because of its late presentation. New technologies now provide simpler, faster, more reliable, and more sensitive tests for viral diagnosis; additionally, antiviral treatment is now available.

Pathophysiology

Viruses are agents that cause infection or cofactors in the development of rheumatic diseases. Viral infection depends on host and viral factors. Host factors are very important and include age, sex, genetic background, infection history, and immune response. Viral factors include the mode of host entry, tissue tropism, replication, the effects of cytokines, the ability to establish persistent or latent viral infections, and alterations of host antigens. Infected cells can undergo apoptosis (programmed cell death).

The immune complexes from an antibody response can be deposited at sites of viral infection or in the synovium. Virus-induced autoimmunity, polyclonal B-cell activation, and immunodeficiency may result in opportunistic infection, largely because of an inability of the immune system to eliminate the virus (eg, HIV, human T-lymphotropic virus 1 [HTLV-I], hepatitis C virus [HCV]). Molecular mimicry may cause abnormal self-reactivity by altering immune tolerance.¹

Frequency

United States

Although not uncommon, the exact incidence and prevalence rates of viral arthritis are unknown and vary with the type of virus and the age range of specific population groups. However, approximately 2.7 million people are infected with HCV in the United States, and perhaps 0.01% of the population is infected with hepatitis B virus (HBV).

International

Although precise international incidence and prevalence rates are unknown, viral arthritis occurs worldwide. The rate of HBV infection is higher in Asia (China, 10% of the population), the Mideast, and sub-Saharan Africa. HCV infection rates are higher in Africa and Asia.

Mortality/Morbidity

The major morbidity of viral arthritis is dysfunctional joints. The mortality rate depends on the type of virus and duration of infection.

Race

Viral arthritis has no recognized racial or ethnic predilection.

Sex

Parvovirus B19 infection is more common in women than in men. Whether hepatitis A virus or HCV has a predilection for either sex is unknown.

Age

Adulthood viral infection rates may be higher than in childhood or vice versa, depending on the virus. HBV infection rates in childhood may be as high as 5% annually. In adulthood, HBV is transmitted through sexual activity or needle exposures. Children are more susceptible to infection with parvovirus B19 than adults, although arthritis rarely occurs in children. Up to 60% of adults have serologic evidence of past parvovirus B19 infection.

Clinical

History

Viral arthritis occurs during the viral prodrome, when the characteristic rash develops. In the United States, patients with the most common viral arthritides generally present with symmetrical small-joint involvement, although different patterns of joint and soft-tissue involvement occur with different viral infections. In all instances, the arthritis associated with viral infections is nondestructive and does not lead to any currently recognized form of chronic disease.

• Parvovirus B19: Discovered in 1975, parvovirus B19 is a small, single-stranded DNA virus that replicates in dividing cells and thus has a remarkable tropism for human erythroid progenitor cells. Parvovirus B19 may be responsible for approximately 12% of the cases of sudden-onset polyarticular arthritis, especially in adults with frequent exposure to children, such as schoolteachers and pediatric nurses, who have a 50% risk of acquiring infection. Outbreaks of erythema infectiosum commonly occur in late winter and spring, but the condition can be observed during summer and fall, with sporadic cases occurring throughout the year.
• Clinical features in children
• Up to 70% are asymptomatic.
• A few may have flulike symptoms (eg, fever, headache, sore throat, cough, anorexia, vomiting, diarrhea, arthralgia).
• A bright red rash is typically noted, often characterized as "slapped cheeks" (see Images 1-2).
• Joint symptoms are rare (5-10%).
• Clinical features in adults
• Rash is rare.
• Joint symptoms occur in up to 60%. Arthralgia is more common than frank arthritis. Arthralgia is usually self-limited; symmetrical; and in peripheral small joints, hands (ie, proximal interphalangeal and metacarpophalangeal), wrists, knees, and ankle joints, with prominent morning stiffness and swelling.
• Parvovirus B19 is emerging as a pathogen responsible for several diseases, including erythema infectiosum (fifth disease), transient aplastic crisis (especially in patients with sickle cell disease, thalassemia, or HIV-induced anemia), and fetal hydrops in infected mothers.
• Rare clinical features
• Henoch-Schönlein purpura is rare but possible.³
• Thrombotic thrombocytopenic purpura is unlikely but may be present.
• Polyarteritis nodosa is rare.
• Wegener granulomatosis is possible but rare.
• Transmission
• Respiratory secretions are a vector for transmission.
• Blood products, especially clotting factor precipitants, are modes of transmission.
• Vertical transmission may occur from mother to fetus. The highest morbidity to the fetus is during the first or second trimester.
• Hepatitis A virus: This infection accounts for 10-14% of cases of viral arthritis. Arthralgia and skin rash occur during the acute phase. Transmission is via the fecal-oral route.
• Hepatitis B virus: HBV is an enveloped, double-stranded DNA virus. HBV infection causes 20-25% of cases of viral arthritis.
• Clinical features
• Symmetric arthritis may be migratory or additive; the hand and knee joints are most commonly affected. Significant morning stiffness and fusiform swelling are associated with HBV-induced arthritis.
• Arthritis and urticaria may precede jaundice by days to weeks and may persist several weeks after jaundice resolves.
• Recurrent polyarthralgia or polyarthritis can occur in patients with chronic active hepatitis or chronic HBV viremia.
• Polyarteritis nodosa may be associated with chronic HBV viremia.
• Patients may have arthritis-dermatitis syndrome.
• Nephropathy has been described.
• Systemic necrotizing vasculitis is also a clinical feature.
• Transmission: This can be parenteral or sexual.
• Hepatitis C virus: HCV is an enveloped, single-stranded RNA virus. HCV infection occurs worldwide.
• Clinical features
• HCV infection causes a rapidly progressive acute arthralgia (but rarely arthritis) in a rheumatoid distribution, affecting the hands, wrists, shoulders, knees, and hips.
• Myalgia is common.
• Essential mixed cryoglobulinemia, a triad of arthritis, palpable purpura, and cryoglobulinemia, is associated with HCV in most cases.
• Necrotizing vasculitis with cryoglobulinemia is a clinical feature.
• Essential mixed cryoglobulinemia type II or III is associated with more severe skin disease, such as Raynaud phenomenon, purpura, livedo-reticularis, distal ulcers, gangrene, and peripheral neuropathy.
• Sjögren syndrome has been described in numerous patients with HCV infection.
• Several recent reports have described a possible association between fibromyalgia and HCV infection.
• Transmission: This can be parenteral or, uncommonly, sexual.
• Rubella virus: This virus is the sole member of the Rubivirus genus (Togaviridae family) and is a single-stranded RNA virus. Rubella virus naturally infects humans, primarily women, and transmission is by nasopharyngeal secretions, with peak incidence in late winter and spring. Approximately 50-75% of rubella virus infections are symptomatic; the rest are subclinical.
• Clinical features (in both children and adults)
• Patients have a low-grade fever, malaise, and coryza.
• Rash (acute mild-to-severe viral exanthema [maculopapular rash]) appears first on the face, then the trunk and upper extremities, and then lower extremities, sparing the palms and soles.
• Significant lymphadenopathy (posterior cervical, postauricular, and occipital) may be noted.
• Arthritis is usually sudden in onset 1 week before or after the rash. Morning stiffness is symmetric and polyarticular in distribution (eg, fingers, knees, wrists), brief in duration (a few days to weeks), and without residua.
• Arthritis may also occur within a few weeks of vaccination by attenuated rubella virus, which is similar to that of natural infection. The HPV77/DK12 strain is the most arthrogenic of the vaccine strains available in the United States. The RA27/3 strain is used currently and causes postvaccination joint symptoms in approximately 15% of recipients.
• In children, 2 syndromes, with either natural infection or vaccination, may occur. In "arm syndrome," a brachial radiculoneuritis causes arm and hand pain and dysesthesias that worsen at night. In "catcher's crouch" syndrome, a lumbar radiculoneuropathy causes popliteal fossa pain upon arising in the morning. Both syndromes occur 1-2 months after vaccination. The first episode may last up to 2 months, but recurrence is usually shorter in duration. Catcher's crouch syndrome may recur for up to a year but causes no permanent damage.
• Transmission: It is transmitted via nasopharyngeal secretions, with a peak incidence in late winter and spring.
• Alphaviruses: These viruses are a genus of the Togaviridae family. Approximately 5-6 types of alphavirus infection cause rheumatic symptoms and fever as major features. All are mosquito-borne. Although alphaviruses are not endemic in the United States, an outbreak of West Nile virus has recently spread across the country. Arthralgia is common with West Nile virus infection (76%), but arthritis has not been described.
• Geographic distribution: The distribution includes Chikungunya (east Africa, India, Southeast Asia, Philippines), O'nyong-nyong (east Africa), the Ross River (Australia, New Zealand, South Pacific islands), Mayaro (South America), Sindbis (Europe, Asia, Africa, Australia, Philippines), and the Barmah Forest (Australia).
• Clinical features
• Fever has been reported, with temperatures from 102.2-104°F (39-40°C)
• Arthritis or a migratory polyarthralgia of the small joints of the hands, wrists, elbows, knees, feet, and ankles occurs, along with stiffness and swelling. The arthritis is generally symmetric and polyarticular. In most alphavirus infections, joint symptoms resolve over 3-7 days, but they can persist for more than a year, albeit with no evidence of permanent joint damage.
• Maculopapular rash may be itchy to some patients.
• Retroviruses
• Human immunodeficiency virus
• HIV infection is associated with several rheumatic manifestations. The most common (25-40%) is arthralgias.
• Others include psoriatic arthritis, painful articular syndrome (10%), undifferentiated spondyloarthropathy, inflammatory myopathy, systemic vasculitis, diffuse infiltrative lymphocytosis syndrome (5%), fibromyalgia (30%), avascular necrosis, and gout.
• Infections may include septic arthritis, osteomyelitis, or pyomyositis or other conditions may be related to soft-tissue rheumatism (eg, tendinitis, bursitis).
• Arthritis (ie, arthralgia, arthritic syndromes) in association with HIV infection has been reported in the United States, Europe, and Africa. Arthritis can occur at any stage of HIV infection. The pattern of HIV-associated arthritis is similar to that of other viral disorders, with an acute onset, short duration, recurrences, and no erosive changes. Interestingly, patients infected with HIV are not at an increased risk for the development of septic arthritis, but they do have an increased frequency of pyomyositis.
• Diffuse infiltrative lymphocytosis syndrome resembles Sjögren syndrome with sicca symptoms, salivary gland enlargement, and lymphocytic infiltration involving the lungs, gastrointestinal tract, and kidneys. In contrast to Sjögren syndrome, the lymphocytes infiltrating these sites are predominantly CD8⁺ (rather than CD4⁺) T cells.
• Reactive arthritis in association with HIV infection occurs in 0.5-3% of cases. Oligoarthritis of the lower extremities and urethritis is common, but conjunctivitis is rare. Severe erosive arthritis is possible and can be very debilitating. The frequency of HLA-B27 in HIV-infected patients with reactive arthritis is the same as that found in patients with reactive arthritis without HIV infection.
• Psoriasis and psoriatic arthritis tend to occur late in the course of HIV infection. This is often severe.
• Human T-lymphotropic virus 1: HTLV-1 is a type C retrovirus (an RNA virus in the Oncovirinae subfamily). It infects millions of people worldwide, particularly in the Caribbean, southern Japan, South Africa, and South America. HTLV-1 is transmitted by breast milk, sexual intercourse, and blood products. HTLV-1 infection is associated with Sjögren syndrome and the following diseases:
• Adult T-cell leukemia/non-Hodgkin lymphoma may develop, with a 5% lifetime risk, and is commonly associated with hypercalcemia and skin involvement.
• Chronic inflammatory syndromes develop at a lifetime risk of 2%. These include a seronegative oligoarthritis or polyarthritis with tenosynovitis and nodules with fibrinoid necrosis. Other syndromes include polymyositislike disease, dermatitis, uveitis, or transverse myelitis (known as tropical spastic paraparesis).
• Other viruses: Several patients have been discovered to have infections with other viruses that can cause arthritis, as follows:
• Epstein-Barr virus: This infection is usually associated with polyarthralgia, but monoarthritis of the knee and ruptured Baker cysts may occur.
• Varicella-zoster virus: This infection in children rarely develops into pauciarticular arthritis.⁴
• Mumps virus: In infected adults, it is associated with small or large joint synovitis that lasts for several weeks. Arthritis may precede or follow parotitis by up to 4 weeks.
• Adenovirus or coxsackieviruses A9, B2, B3, B4, and B6: These infections have been associated with recurrent episodes of polyarthritis, pleuritis, myalgia, rash, pharyngitis, myocarditis, and leukocytosis.
• Echovirus: This infection can be associated with polyarthritis, fever, and myalgias.
• Herpes simplex virus or cytomegalovirus: These infections are also rare. Cytomegalovirus arthritis has been reported in patients after bone marrow transplantation. Vaccinia virus has been associated with postvaccination knee arthritis in only 2 reported cases.

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