Viral arthritis



by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit


Information from the Center for Disease Control and Prevention and Medscape

Arthritis may be a symptom of viral illness. The duration is usually short, and it disappears on its own without any lasting effects.

The exact incidence and prevalence rates of viral arthritis are unknown and vary with the type of virus and the age range of the population group. For example, 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).

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.

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

Some examples of viruses that may cause arthritis include:

Parvovirus B19 is a small, single-stranded DNA virus. It may be responsible for causing approximately 12% of the cases of sudden-onset polyarticular arthritis, especially in adults with frequent exposures 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% may be 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"
• 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 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.


Transmission occurs with:

• 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 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 a 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.
• Kidney involvement is described.
• Systemic necrotizing vasculitis is also a clinical feature.


Transmission can be parenteral or sexual.

Hepatitis C virus: HCV is a single-stranded RNA virus. HCV infection occurs worldwide.

Clinical features:

• It 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 which presents with 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.
• Sjögrens syndrome has been described in a number of HCV patients.
• Several recent reports describe a possible association between fibromyalgia and HCV infection.


Transmission can be parenteral or sexual.

Rubella virus 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:

• Patients have a low-grade fever, malaise, cough and flu-like symptoms.
• 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 residual problems.
• 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, two 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 is via nasopharyngeal secretions, with a peak incidence in late winter and spring.

Alphaviruses are not endemic in the United States; however, 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.

Clinical features:

• Fever is 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, but 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.

Reiter’s syndrome 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 Reiter syndrome patients is the same as that found in Reiter syndrome patients of the same race 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. 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.

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.

Viral arthritis occurs during the viral prodrome, when the characteristic rash arises. 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 most instances, the arthritis associated with viral infections is nondestructive and does not lead to any currently recognized form of chronic disease.

On physical examination, the patient may show signs of joint inflammation. A serology for viral agents may be performed.

Diseases to rule out when viral arthritis is suspected are:

Acute Rheumatic Fever

Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy

Aplastic Anemia

Cryoglobulinemia

Lyme Disease

Polymyositis

Psoriatic Arthritis

Rheumatoid Arthritis

Sjogren Syndrome

Systemic Lupus Erythematosus



Laboratory studies that are helpful are:



For Parvovirus:

• CBC count (to assess hemoglobin, neutrophils, lymphocytes)
• High immunoglobulin M antibody levels 4-6 days after the initial viremia
• Viral B19 DNA by polymerase chain reaction
• Immunoglobulin G antibody titer has little diagnostic significance
• Low-to-moderate titer values for rheumatoid factor, anti-DNA, antinuclear, and anticardiolipin antibodies possible in some patients


Hepatitis A virus

• Elevated bilirubin and transaminases values
• Immunoglobulin M–specific anti–hepatitis A virus


Hepatitis B virus

• Elevated bilirubin and transaminases values (may be normal in early stage of disease when arthritis is present)
• Serum hepatitis B surface antigen, hepatitis B early antigen, anti–hepatitis B surface antigen immunoglobulin M (indicates acute infection), viral DNA, polymerase


Hepatitis C virus

• Elevated bilirubin and transaminase values (Normal transaminase levels do not exclude HCV infection.)
• Anti-HCV
• HCV-RNA by polymerase chain reaction methods
• Cryoglobulins, rheumatoid factor


Rubella virus

• Anti–rubella virus immunoglobulin M (peaks 8-21 d after symptoms, then wanes by 5 wk)
• Anti–rubella virus immunoglobulin G (rises rapidly over a period of 1-3 wk and is of long duration)
• More recently, rubella virus has been isolated from lymphocytes and synovial fluid of patients who had vaccine-induced disease or who experienced rubella virus–associated arthritis years earlier.


Alphaviruses: Diagnosis is confirmed by specific serology results.

Human immunodeficiency virus: Generally, laboratory abnormalities are common but nonspecific in persons with HIV infection.

Elevated levels of serum immunoglobulins, moderate elevation of erythrocyte sedimentation rate, circulating immune complexes, low-grade complement activation, low-titer antinuclear antibody, rheumatoid factor, false-positive test result for syphilis and anticardiolipin antibodies, and lupus anticoagulants

Human T-lymphotropic virus: Diagnosis of HTLV-1 is achieved by the detection of antibodies with enzyme-linked immunosorbent assays, with confirmation by Western blot and the observation of "flower cells" on the peripheral smear.



X-ray findings depend on the condition. Most of the virally associated arthropathies are nonerosive and show only soft tissue swelling. However, with HIV-related seronegative or psoriatic-type arthropathy, erosions, ankylosis, narrowing of joint spaces, whittling, osteolytic lesions, periostitis, sacroiliac joint-space widening, and syndesmophyte formation can be seen.

Aspiration of the joint is useful to help rule out other conditions such as crystal arthropathy or bacterial infection.

In general, viral arthritis is mild and patients require only symptomatic treatment with analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs). Occasionally, a brief course of low-dose prednisone may be used.

Parvovirus B19: Treatment is symptomatic with analgesics and NSAIDs. In severe cases, aspiration of fluid from the affected joint may relieve pain.

Hepatitis A virus: Treatment is symptomatic with analgesics and NSAIDs. Prophylaxis for contacts is an important element of management.

Hepatitis B virus: No evidence indicates that early therapy for acute HBV infection with interferon alfa or antiviral agents decreases the rate of chronicity or speeds recovery. Most patients with acute icteric HBV infection recover without residual injury or chronic hepatitis. Focus management of acute HBV infection on avoidance of further hepatic injury and prophylaxis of contacts.

Hepatitis C virus: Administer interferon alfa-2b (3-5 million U 2-3 times/wk for 6 mo). Combination therapy with ribavirin (1000-1200 mg/d) is recommended and has been shown to yield better response rates. Patients with complications of cryoglobulinemia are best treated with antiviral therapy. However, corticosteroids and cyclophosphamide may be required initially for patients with more active, severe vasculitic complications.

Rubella virus: Treatment is symptomatic with analgesics and NSAIDs. Steroids at low-to-moderate doses to control symptoms and viremia are suggested by some investigators.

Alphaviruses: Treatment is symptomatic with analgesics and NSAIDs, but avoid aspirin in order to prevent a hemorrhagic component with alphavirus rashes. Chloroquine phosphate (250 mg/d) has been used when NSAIDs are not effective.

Human immunodeficiency virus
Use a combination of newer antiretroviral therapy.
Treatment is symptomatic with analgesics and NSAIDs. Administer sulfasalazine and methotrexate for patients with conditions refractory to NSAID therapy.
Prednisone, antimalarials, and other agents have been successfully used in patients with polymyositis, Reiter syndrome, Sjögrenlike syndrome, psoriatic arthritis, and vasculitis.
Antiretroviral and prophylactic therapy, sulfamethoxazole-trimethoprim, and pentamidine help improve associated rheumatic symptoms.
Intravenous immune globulin, interleukin-12, interleukin-2, interferon gamma, and/or sargramostim may be effective for some HIV-infected patients with arthritis.


Human T-lymphotropic virus 1: Treatment options are very poor.

The outcome is usually good for most common viruses. Most arthritis disappears within several days to weeks with resolution of the viral illness.

There is no known way to prevent viral arthritis.




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