Imaging demonstrates musculosketal effects of HIV

In targeting the immune system, the human immuno-deficiency virus (HIV) compromises host defense mechanisms. This breach in immunity results in a wide spectrum of disease throughout the body. Musculoskeletal manifestations of HIV constitute an unusual but important group of inflammatory and rheumatic conditions, infections, and neoplasms.

The presentation and radiological features of HIV-related musculoskeletal disorders are similar to those seen in the general population. However, these disorders may present atypically, occur at unusual sites, and in the case of infection, be caused by uncommon organisms. The introduction of highly active antiretroviral therapy (HAART) has altered the disease spectrum, and the drugs themselves have musculoskeletal side effects.

Myositis can occur in HIV-positive patients during seroconversion or at any time during the course of the illness, owing to the virus itself. It may also occur secondary to drug therapy, such as zidovudine (AZT), or following opportunistic infections, such as toxoplasmosis.1 Patients present with proximal muscle weakness and elevated serum creatine kinase. Imaging features include evidence of inflammation with hyper-reflectivity in affected muscles on ultrasound, low density on CT, and increased signal on T2-weighted MRI.2 A biopsy of the abnormal tissue may be required if the imaging features of muscle inflammation are not specific for myositis. Similar appearances can also be seen in pyomyositis and fasciitis.

Psoriatic arthropathy occurs with increased frequency in the HIV-positive population. Estimates of prevalence range from 1% to 32%.3 Clinically, psoriatic arthropathy is characterized by nail and skin changes and enthesitis. The disease is asymmetrical and commonly affects small joints of the hands and feet, sacroiliac joints, and the spine. Large joints are often spared. Radiological features include distal predominance with soft-tissue swelling, osteolysis, marginal erosions, and pencil-in-cup deformity. Other features include bony proliferation (adjacent to erosions and at tendon/ligament insertions), periosteal new bone, ankylosis, sacroiliitis, and spondylitis with paravertebral ossification (Figure 1).

Reiter's syndrome is strongly associated with HLA-B27 in both HIV-positive and uninfected populations.2 The incidence of this reactive arthropathy in the HIV population remains controversial. No evidence exists that HIV is an etiological factor.4-6 Reiter's syndrome can occur at any stage of the disease. The classic triad of urethritis, conjunctivitis, and arthritis is seen less often than the incomplete form, which is characterized by enthesitis, spondylitis, and erosive, seronegative oligoarticular asymmetric arthritis. Extra-articular manifestations, such as nail changes, circinate balanitis, and keratoderma blennorrhagia, are common. Radiological appearances are similar to psoriatic arthritis, although feet and ankles are more often involved than hands.7 The most common finding in the foot is enthesopathy, which can involve the Achilles tendon, plantar fascia, anterior and posterior tibial tendons, and extensor tendons. The term "AIDS foot" describes what happens when patients with painful heels, due to enthesopathy, adopt a wide gait to avoid walking on the lateral aspect of the foot.

An acute rheumatoid-like symmetrical polyarticular erosive arthritis may be seen in the late stages of HIV disease. The disease behaves clinically like rheumatoid arthritis, although patients will be rheumatoid-factor negative and negative for HLA-B27.1 An oligoarticular form of HIV-associated arthritis, with painful swelling to large joints (especially knees and ankles), may be seen late in the course of HIV infection.3 Symptoms can last from one week to six months. HIV can be isolated from thickened synovium.

Painful articular syndrome typically affects the knees with severe pain of short duration lasting for up to 48 hours. Radiographic features are nonspecific and include osteopenia and joint effusions.7

INFECTION

Cellulitis is an infection of the superficial subcutaneous tissues characterized by swelling, erythema, and pain. Local trauma and predisposing conditions, such as lymphedema, make cellulitis and soft-tissue abscesses more common in HIV disease. Both CT and MRI demonstrate inflammatory changes in the subcutaneous fat in cases of superficial cellulitis. There is increased attenuation on CT, increased signal on T2-weighted MRI, and diffuse enhancement following contrast administration.

Observation of signal changes in deeper structures, such as fascia or muscles, should lead to fasciitis and myositis being included in the differential diagnosis. Necrotizing fasciitis is characterized by necrosis of superficial and deep tissues, and it requires surgical debridement. Imaging features are similar to cellulitis but are more marked and involve deeper structures, including the fascia and muscles (Figure 2). Fluid collections, thickening of the fascia, and gas in the soft tissues are seen. Areas of necrosis do not tend to show postcontrast enhancement.1

The muscle infection pyomyositis can be fatal if left untreated. It is rare in the general population and tends to occur in the late stages of HIV when CD4 cell counts are less than 200 cells/microL.8 The most common causative agent is Staphylococcus aureus. Mycobacterium tuberculosis pyomyositis is also seen in HIV-positive patients, and as in the non-HIV population, the condition may be more indolent in its presentation compared with bacterial pyomyositis (Figure 3).

Pyomyositis characteristically presents with pain, fever, and stiffening of the affected muscle. This first stage often lasts from one to three weeks. The next stage involves increased pain, fever, and muscle edema. Pus can be aspirated from the affected muscles. The final stage can occur within three weeks of initial diagnosis. It is characterized by frank necrosis and the development of muscle abscesses, with increased risk of septicemia and death.7

Pyomyositis typically involves multiple sites, and imaging plays a crucial role in directing patient management. Therapeutic options are antibiotics, aspiration, and possible surgical debridement. Imaging features of pyomyositis include:

- hyper-reflectivity in affected muscles on ultrasound;

- muscle enlargement, reduced attenuation secondary to edema, and rim enhancement on postcontrast CT;

- low-signal central area with high-signal rim on T1-weighted MRI;

- high signal on T2-weighted MRI and STIR images, with rim enhancement following gadolinium contrast; and

- increased uptake of gallium-67 and indium-111 tagged white blood cells.

Septic arthritis is the most common musculoskeletal infection encountered in HIV-positive patients. It is usual for large weight-bearing joints to be affected. Involvement of unusual sites such as the sternoclavicular joint has also been reported.2

Septic arthritis is characterized by joint effusions, periarticular osteoporosis, cortical erosions, and sclerotic reaction. The joint space may be normal, increased, or decreased, depending on the relative degree of cartilage destruction or effusion. MRI is the most sensitive modality for detecting early changes of septic arthritis. Imaging features include bone marrow edema on both sides of the joint and joint effusions (Figure 4). Aspiration and culture of the joint fluid is necessary to direct antibiotic therapy.

Osteomyelitis is the second most common musculoskeletal infection in HIV-positive patients. This tends to occur in the late stages of HIV with CD4 cell counts less than 250 cells/microL.8 The most common sites of involvement are the spine and long bones, but any bone can be affected. Plain films may be normal in the early stages of osteomyelitis. X-rays may demonstrate soft-tissue swelling, cortical destruction, and a periosteal reaction after about 10 to 14 days. MRI is useful in the early stages and characteristically demonstrates bone marrow edema, cortical destruction, and adjacent soft-tissue mass (Figure 5).

Bacillary angiomatosis is caused by opportunistic infection with the Rickettsia-like organisms Bartonella henselae or Bartonella quintana. Lesions are characterized by vascular proliferation. They affect the skin, subcutaneous tissues, solid organs (peliosos), lymph nodes, muscle (pyomyositis), and bone (osteomyelitis) and occur predominantly in HIV-positive patients with CD4 cell counts less than 100 cells/microL.8 Bony involvement is typically painful and is characterized by osteolytic lesions, cortical destruction, periosteal reaction, and an overlying soft-tissue mass.7

Biopsy is often required to differentiate bacillary angiomatosis from Kaposi's sarcoma, lymphoma, and bacterial osteomyelitis. Correct diagnosis is essential, given that bacillary angiomatosis can be treated effectively with appropriate antibiotics.

NEOPLASMS TO NECROSIS

Kaposi's sarcoma is the most common neoplasm in HIV patients and is an AIDS-defining illness. Its incidence is much higher in the HIV-positive population than in the uninfected population. Individuals without HIV rarely contract Kaposi's sarcoma.

Lesions most frequently involve the skin in the early stages of HIV infection. Multi-organ involvement tends to occur in the late stages of HIV, with CD4 cell counts below 200 cells/microL. Kaposi's sarcoma will typically affect the lymph nodes, gastrointestinal tract, liver, and lung.3 Bone lesions are less common. Plain-film x-rays may demonstrate lytic cortical lesions and periosteal reaction, but they may also be normal (Figure 6). A biopsy may be required to confirm diagnosis. Kaposi's sarcoma can be treated with chemotherapy and radiotherapy, but the prognosis is poor.

In the HIV-positive population, non-Hodgkin's lymphoma, which is typically of the high-grade B-cell type, is more aggressive and demonstrates earlier systemic dissemination than in uninfected individuals. It typically occurs in the late stages of HIV, with CD4 counts less than 150 cells/microL, and is also an AIDS-defining illness.3

The prevalence of non-Hodgkin's lymphoma among AIDS patients in the post-HAART era is controversial. Data can be found from large population studies to support both an increase and a decrease in incidence.9-11 Between 60% and 95% of HIV-positive patients will present with extranodal disease, in contrast with the principally intranodal pattern seen in lymphomas in the general population. Common areas of involvement are the bone marrow, mucocutaneous sites, gastrointestinal tract, and central nervous system.2

The radiological appearance of extranodal involvement can mimic osteomyelitis, tuberculosis, bacillary angiomatosis, pyomyositis, multiple myeloma, and Kaposi's sarcoma. Bone involvement is characterized by ill-defined lytic lesions with cortical destruction, sclerotic foci, and, less commonly, periosteal reaction (Figure 7). There may also be an associated soft-tissue mass.

MRI can be useful in assessing bone marrow involvement, although a biopsy is required for definitive diagnosis. Treatment involves chemotherapy and radiotherapy, but the prognosis is poor.

Avascular necrosis is characterized by bone death and collapse. The etiology, which is multifactorial, may be due to steroids, radiotherapy, and possibly HAART in HIV-positive patients. Although the femoral head is the most susceptible, multiple joints can be involved. The most common presenting symptom is pain.

Plain films can be normal in early stages of avascular necrosis. They may later show evidence of sclerosis, subchondral lucency, and loss of joint space. Bone scans typically show a region of high uptake surrounding a cold area. This reflects the interface between dead and hypervascular bone.

MRI is the most sensitive modality for diagnosing avascular necrosis, which has a similar appearance on MRI regardless of a patient's HIV status (Figure 8). The double-line sign on T2-weighted MRI is pathognomonic for avascular necrosis due to the low-signal region of infarction adjacent to hypervascular granulation tissue (Figure 9).3

In conclusion, HIV infection may result in a wide spectrum of musculoskeletal disorders. These can be divided into inflammatory, infective, and neoplastic conditions. Imaging plays a crucial role in the diagnosis and management of these conditions.

References

1. Restrepo CS, Lemos DF, Gordillo H, et al. Imaging findings in musculoskeletal complications of AIDS. Radiographics 2004;24(4):1029-1049.

2. Burke S, Healy J. Musculoskeletal manifestations of HIV infection. Imaging 2002;14:35-47.

3. Tehranzadeh J, Ter-Oganesyan RR, Steinbach LS, et al. Musculoskeletal disorders associated with HIV infection and AIDS. Part II: Non-infectious musculoskeletal conditions. Skel Radiol 2004;33(6):311-320.

4. Hochberg MC, Fox R, Nelson KE, Saah A. HIV infection is not associated with Reiter's syndrome: data from the Johns Hopkins Multicenter AIDS cohort study. AIDS 1990;4(11):1149-1151.

5. Clark MR, Solinger AM, Hochberg MC. Human immunodeficiency virus infection is not associated with Reiter's syndrome. Data from three large cohort studies. Rheum Dis Clin N Am 1992;18(1):267-276.

6. Espinoza LR, Jara LJ, Espinoza CG, et al. There is an association between HIV and spondyloarthropathies. Rheum Dis Clin North Am 1992;18(1):257-266.

7. Major N, Tehranzadeh J. Musculoskeletal manifestations of AIDS. Radiol Clin North Am 1997;35:1167-1189.

8. Tehranzadeh J, Ter-Oganesyan RR, Steinbach LS, et al. Musculoskeletal disorders associated with HIV infection and AIDS. Part I: Infectious musculoskeletal conditions. Skel Radiol 2004;33(5):249-259.

9. Ives NJ, Gazzard BG, Easterbrook PJ. The changing pattern of AIDS-defining illnesses with the introduction of HAART in a London clinic. J Infect 2001;42(2):134-139.

10. Dove GJ, Li Y, McDonald A, et al. Impact of highly active retroviral therapy (HAART) on individual AIDS-defining illness incidence and survival in Australia. J Acquired Immune Def Syn 2002;29(4)388-395.

11. Wolf T, Brodt HR, Fichtlscherer S, et al. Changing incidence and prognostic factors of survival in AIDS related NHL in era of HAART. Leuk Lymphoma 2005;46(2):207-215.

Dr. Wessely is a specialist registrar in radiology, Dr. Lee is a consultant radiologist, and Dr. Healy is a consultant radiologist, all at the Chelsea and Westminster Hospital in London.