Viral Arthritis Clinical Presentation

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 below).Viral arthritis. Typical "slapped cheek" appearance. Courtesy of Brenda Moroz, MD, Montreal Children's Hospital. Viral arthritis. "Slapped cheeks" with typical reticulated erythema of arms. Courtesy of Brenda Moroz, MD, Montreal Children's Hospital.
    • 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.^[2]
    • 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),^[3] 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.^[4]
    • 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.^[5]
  • 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.