The human retrovirus HIV infects an estimated 33 million people worldwide. Other retroviruses (eg, human T-lymphotropic virus type I) have been reported to be associated with inflammatory arthropathies, so it is not surprising that a number of rheumatologic manifestations have been described in HIV-infected persons (Table 51–1). These include various arthropathies, muscle diseases, bone disorders, symptoms and signs mimicking Sjögren syndrome, and systemic vasculitis. For some of these disorders, a clear pathophysiologic association with HIV has been established. For others, true relationships remain speculative. Geographic predisposition among HIV-infected persons to certain rheumatologic conditions is suggested by a number of studies.

Essentials of Diagnosis

• Diagnosis of HIV infection is made by serologic tests (enzyme-linked immunosorbent assay) and confirmed by Western blot.
  
• HIV causes nonspecific B-cell activation resulting in a polyclonal hypergammaglobulinemia and a high frequency of false-positive autoantibody tests.
  
• Rheumatologic manifestations include arthralgias, increased severity (and possibly increased incidence) of seronegative spondyloarthropathies, musculoskeletal infections, osteopenia/osteoporosis, and avascular bone necrosis.
  
• Myalgias with minimal laboratory evidence of muscle damage are consistent with several conditions, including fibromyalgia, the HIV wasting syndrome, and antiretroviral toxicity.
  
• Limited data suggest that highly active antiretroviral therapy (HAART) may be associated with several rheumatologic complications including arthralgias, myopathies, and abnormalities in bone mineralization.
  
• Concomitant use of HAART and immunosuppressive agents requires careful consideration of drug interactions, heightened toxicities, and difficulty in monitoring certain clinical HIV-related parameters.

General Considerations

Patients with HIV have heightened activation of the B-cell compartment and a high prevalence of polyclonal hypergammaglobulinemia. Partly as a consequence of this, the frequency with which autoantibody production is detected in patients with HIV is increased compared with healthy persons. The interpretation of positive autoantibody assays (eg, antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibodies) may be complicated in patients with HIV. Correlation between the laboratory and clinical findings is important.

Pathogenesis

HIV infection may modulate the host immune response contributing to the development of various rheumatic manifestations. Painful articular syndrome and HIV-associated arthritis represent distinct clinical syndromes that develop during the course of HIV infection, suggesting a direct role for HIV. The role of HIV in reactive arthritides, undifferentiated spondyloarthropathies, and musculoskeletal infections is most likely indirect, either by increasing susceptibility or influencing the clinical course of these diseases in susceptible patient groups. A unique spectrum of rheumatic manifestations has been recently recognized among HIV-infected persons treated with highly active antiretroviral therapy (HAART). Immune reconstitution after such therapy may be responsible for some of these manifestations.

HIV Painful Articular Syndrome

This syndrome is characterized by debilitating arthralgias that are often sufficiently severe to precipitate emergency department visits. Painful articular syndrome has been reported to occur in up to 10% of HIV-infected persons. Symptoms last from 2–24 hours and usually resolve spontaneously. The joint complaints are usually oligoarticular and asymmetric. The affected joints—most commonly the knees, but elbows and shoulders may also be affected—are free of any signs of inflammation on examination. Radiographs often reveal nonspecific findings such as periarticular osteopenia. Targeting symptoms using nonsteroidal anti-inflammatory drugs or opioids and reassurance is usually successful. If symptoms do not improve within 1–2 days, reconsidering the diagnosis is mandatory.

HIV-Associated Arthritis

A subacute asymmetric oligoarthritis that usually affects the large joints (most commonly the knees, but ankles and wrists may also be involved) may occur in patients with more advanced HIV infection. This form of arthritis usually has a self-limited course ranging from 1 week up to 6 months. The prevalence has been reported in the range of 3–25% of HIV-infected patients, the higher prevalence coming from a cohort in Zambia, suggesting a possible geographic predisposition. The HIV has been detected in synovial fluid, which is consistent with (but not diagnostic of) an etiologic role for the virus itself. Suppression of viral replication using HAART may be beneficial for the treatment of this disorder, but controlled trials are lacking. Treatment has centered on nonsteroidal anti-inflammatory drugs, and some reports note benefit from low-dose glucocorticoids and hydroxychloroquine. The incidence of this condition appears to have decreased following the introduction of HAART.

HIV-Associated Acute Symmetric Polyarthritis

Acute symmetric polyarthritis affects the small joints of the hands, and its manifestations resemble rheumatoid arthritis. Findings include periarticular osteopenia, joint-space narrowing, swan-neck deformity, and ulnar deviation. Rheumatoid factor is usually negative. Studies have reported therapeutic success with the use of gold.

Adhesive Capsulitis

An association between the use of protease inhibitors and the development of subacute progressive shoulder pain with limited range of motion has been suggested (Table 51–2). Typically, symptoms begin a year after the medications are started and usually resolve within 7–12 months. Because radiographic findings are usually lacking, the diagnosis is clinical. Physical therapy, nonsteroidal anti-inflammatory drugs, and the judicious use of intra-articular glucocorticoids (see Chapter 2) have been successfully used to treat this condition. Although the association with protease inhibitors is far from convincing, physicians may consider switching the HAART regimen to a non–protease inhibitor class (eg, nonnucleoside reverse transcriptase inhibitors). If that is not an option, the data suggest that symptoms tend to resolve despite persistent use of protease inhibitors.

Psoriatic Arthritis

Psoriasis and psoriatic arthritis may be the initial presentation of underlying HIV infection. Prevalence estimates of psoriasis among HIV-infected patients range from 1–32%, with a tendency for appearance or exacerbation in more advanced stages of HIV infection. Arthritis develops in as many as 30% of HIV patients who have cutaneous psoriasis. The pattern of psoriatic arthritis—polyarticular, asymmetric involvement with dactylitis and enthesopathy—differs from that seen in individuals without HIV in that sacroiliac and axial skeleton involvement initially seems less common. As the natural history of HIV has been altered by new treatments, the axial bony changes commonly seen in persons with psoriasis who are not HIV-infected have been observed among patients living longer than 5 years with psoriatic arthritis. These include unilateral sacroiliitis and bulky spondylitis that skips adjacent vertebral bodies. HIV-associated psoriasis may be refractory to traditional therapy. Guidelines for the treatment of psoriasis in HIV-infected persons have been published by the National Psoriasis Foundation.

Reactive Arthritis & Other Spondyloarthropathies

Spondyloarthropathies in the setting of HIV infection may present with the typical form of reactive arthritis or may have atypical features classified as undifferentiated spondyloarthropathy. The characteristic clinical findings are those of a peripheral arthritis involving the lower extremities and prominent enthesopathy (eg, Achilles tendinitis and plantar fasciitis). Extra-articular manifestations, including eye inflammation, urethritis, and mucocutaneous lesions, are also common. Axial involvement is typically infrequent. The clinical course is unpredictable, although a severe form of erosive polyarthritis has been reported in black patients.

Studies from the late 1980s suggested an increased risk of reactive arthritis in HIV-positive patients. Data from several subsequent cohorts found no change in prevalence between HIV-infected and uninfected patients, suggesting that reactive arthritis was not due to HIV per se but due to the prevalence of high-risk sexual behaviors leading to postvenereal reactive arthritis. Data from sub-Saharan African patients, however, suggest a more complicated relationship. The prevalence of spondyloarthropathies has clearly risen with the increase in HIV infections, with no apparent change in triggers for reactive arthritis. In contrast to seronegative patients, these HIV-positive patients are predominantly HLA-B27 negative and have a more aggressive course of arthritis.

Other Rheumatic Conditions Associated with HIV

Septic arthritis and malignancies are not directly caused by HIV infection, but should be considered when evaluating HIV-infected patients with rheumatologic complaints.

Given the frequency of injection drug use as the primary risk factor for HIV infection, the high incidence of joint infections is not surprising in this subset of patients. As the CD4+ T-cell count drops below 200 cells/mcL, the risk of musculoskeletal infections rises. Staphylococcus aureus is the most common joint pathogen described. Mycobacterial arthritis mainly cause by Mycobacterium avium intracellulare has been reported among patients with a CD4 cell count less than 50 cells/mcL.

Rarely, lymphoma may present as arthritis of a large joint. Data suggest a decreased incidence of lymphoma after the introduction of HAART.