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Journal of the American Academy of Orthopaedic Surgeons 312 Patients infected with the human immunodeficiency virus (HIV) dis- play a wide array of disease pro- cesses secondary to this systemic infection. 1 Multiple organ systems, including the musculoskeletal sys- tem, may be involved; Berman et al 2 studied 101 consecutive patients with HIV infection and found that 71% had bone, joint, or muscle in- volvement. These patients can be significantly disabled and often pre- sent a diagnostic dilemma. Myopa- thies, neuropathies, and arthropa- thies can be difficult to distinguish from each other. Certain infections and inflammatory conditions rarely seen in the general population are more prevalent in this patient popu- lation. Musculoskeletal involve- ment may occur at any phase of HIV infection but is more commonly seen in later stages. 3 Knowledge of these conditions is a prerequisite to effective management of musculo- skeletal complaints in HIV-infected individuals. Acute Infection Phase The signs and symptoms of acute HIV-1 infection usually are noted within days or weeks after expo- sure. Retrospective studies have shown that 85% of acute infections are not clinically silent and that 95% of patients seek medical attention because of symptoms. 1 The most common signs and symptoms are fever, fatigue, and a maculopapular skin rash. Most patients (50% to 70%) also complain of myalgias, arthralgias, and paresthesias, which may be the only symptoms of the acute infection. 1 Although the acute illness may last from only a few days to as many as 10 weeks, it usually subsides within 2 weeks. Acute HIV infection should be included in the differential diagnosis of sudden on- set of arthralgias and myalgias with a compatible history of exposure. 1 Myopathies Pyomyositis In 1885, Scriba 4 first described the formation of abscesses in striated muscle, now known as pyomyositis. Originally called pyomyositis tropi- cans because it was endemic to trop- ical regions, it accounted for up to 4% of all surgical admissions in some African hospitals. 5 This infec- tious disease was rare in more tem- perate climates, with only 50 cases reported before 1981. 6 These cases tended to involve patients who Dr. Biviji is Resident, Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA. Dr. Paiement is Professor, Department of Ortho- paedic Surgery, University of California, San Francisco. Dr. Steinbach is Professor, Depart- ment of Radiology, University of California, San Francisco. Reprint requests: Dr. Paiement, Room 3A36, 1001 Potrero Avenue, San Francisco, CA 94110-0842. Copyright 2002 by the American Academy of Orthopaedic Surgeons. Abstract Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Knowledge of the conditions affecting muscle, bone, and joints in HIV-infected patients is essen- tial for successful management. Myopathies may be caused by pyogenic infection (eg, pyomyositis), idiopathic inflammation (eg, polymyositis), or drug effect (eg, AZT myopathy). Characteristic skeletal infections, such as tuberculosis and bacillary angiomatosis, require a high index of suspicion for accurate diagnosis. Neoplastic processes, such as non-Hodgkin’s lymphoma and Kaposi’s sarcoma, occur more frequently as the immune system deteriorates. Inflammatory and reactive arthropathies are more prevalent in HIV-positive than HIV-negative individuals and include Reiter’s syndrome, psoriatic arthritis, HIV-associated arthritis, painful articular syndrome, acute symmetric polyarthritis, and hyper- trophic osteoarthropathy. Patients with atypical musculoskeletal complaints and a suspected history of exposure should be tested for HIV. J Am Acad Orthop Surg 2002;10:312-320 Musculoskeletal Manifestations of Human Immunodeficiency Virus Infection Ayaz A. Biviji, MD, Guy D. Paiement, MD, and Lynne S. Steinbach, MD Ayaz A. Biviji, MD, et al Vol 10, No 5, September/October 2002 313 were malnourished or immunocom- promised from diseases such as dia- betes, Felty’s syndrome, and lym- phocytic leukemia. In 1987, Watts et al 6 first reported pyomyositis in a British patient with HIV. Pyomyo- sitis has become more prevalent in Western countries because of a growing HIV-infected population, and it is seen more frequently as the immune system deteriorates. 7 Most cases in temperate climates are initially misdiagnosed as muscle strain, contusion, hematoma, celluli- tis, deep vein thrombosis, osteomy- elitis, septic arthritis, or neoplasm. In a series from Hawaii, 8 one patient underwent an en bloc excision for a presumed soft-tissue sarcoma that in fact was pyomyositis. The diag- nosis of pyomyositis should be con- sidered in any HIV-infected individ- ual who presents with systemic symptoms and insidious muscle pain and swelling. Clinical manifestations of pyo- myositis are classified in three stages 9 (Table 1). The first stage is characterized by cramplike pain localized to one muscle group, along with induration and low-grade fever. Chiedozi 9 reported that this entity occurred in the quadriceps muscle group in 75% of 112 patients. Multiple areas of involvement were seen in 30% to 40% of patients. The soft tissues in the first stage have a “wooden” stiffness on palpation. The second stage is marked by in- creasing pain, high-grade fever, and formation of an abscess within the muscles. Finally, in the third stage, the patient becomes septic and the muscles, necrotic. If the patient is not adequately treated, septic shock and death may result, usually within 3 weeks of the onset of initial symp- toms. The mortality rate in the series reported by Chiedozi was 1%. 9 More recently, other series 10 have reported a mortality rate as high as 20%. An elevated erythrocyte sedi- mentation rate usually is noted, and serum creatine kinase (CK) levels are often normal, even in advanced cases of myonecrosis. Blood cul- tures were positive in 5% of cases in the largest case series. 6 Staphylo- coccus aureus is the most common pathogen (90% of cases) but other organisms, including Streptococcus pyogenes, Mycobacterium tuberculosis, Nocardia asteroides, and Cryptococcus neoformans, have been identified. 6 Imaging modalities, including ultrasound, contrast-enhanced com- puted tomography (CT), and mag- netic resonance imaging (MRI), help identify the fluid collection and delineate the extent of the infection. Increased radionuclide uptake of gallium 67– and indium 111–tagged white blood cells may allow rough localization to a particular muscle group. Contrast-enhanced CT can demonstrate a well-defined abscess as a rim-enhancing low-attenuation mass within a muscle belly (Fig. 1). MRI is especially useful in earlier stages when the clinical diagnosis may be difficult and confusing. A rim of increased signal intensity around a central isointense area rela- tive to normal muscle can be seen on T1-weighted MRI (Fig. 2, A). This central area appears hyperintense on T2-weighted images (Fig. 2, B). The exact etiology of pyomyositis is debatable. Miyake 11 showed in a canine model that simple inocula- tion of a muscle with sublethal doses of S aureus did not cause pyomyo- sitis. However, the same inoculation of traumatized muscle resulted in the formation of abscesses, leading to the hypothesis that pyomyositis develops in patients with preexist- ing muscle damage who experience transient bacteremia. Muscle injury may result from nutritional deficien- cies, azidothymidine (AZT)-induced mitochondrial injury, opportunistic infections, or direct viral invasion of muscle tissue in HIV-infected indi- viduals. 5 Some have theorized that an antecedent parasitic infection of Table 1 Clinical Stages of Pyomyositis 9 Clinical Stage Symptoms Clinical Signs Workup and Treatment I Early invasive Muscle pain Induration, CBC, ESR, MRI, (often low-grade blood cultures, quadriceps) fever parenteral antibiotics II Suppurative Severe pain, Abscess Contrast-enhanced malaise formation, CT scan, ultrasound, high fever surgical drainage III Late Shock, death Extensive Resuscitation, necrosis aggressive débridement CBC = complete blood count, ESR = erythrocyte sedimentation rate Figure 1 An HIV-infected patient with pyomyositis (Salmonella) of his upper arm. Axial CT image demonstrates an infiltrative process (arrow) of the triceps muscle group. Musculoskeletal Manifestations of HIV Infection Journal of the American Academy of Orthopaedic Surgeons 314 muscle may set up the nidus for infection in tropical regions, where people often walk barefoot. 5 Neu- trophil dysfunction in HIV-infected patients may contribute to the pre- disposition to bacterial infection. Decreased chemotaxis, phagocyto- sis, and leukocyte bactericidal activi- ty also have been demonstrated in in vitro studies. 6 An increased fre- quency of a Staphylococcus carrier state relative to the general popula- tion also has been suggested in these patients. 12 Early recognition and aggressive management with par- enteral antibiotics and surgical drainage are the keys to treatment of pyomyositis. Polymyositis Polymyositis (idiopathic inflam- matory myositis) may be the first manifestation of HIV. 13 This condi- tion is characterized by bilateral, symmetrical proximal muscle weak- ness associated with elevated serum CK levels. Its unique characteristics make polymyositis distinguishable from pyomyositis, which usually occurs in advanced stages of HIV. Polymyositis may be related to a direct invasion of muscle tissue by the virus, causing a cytopathic effect and subsequent muscle fiber necro- sis. Dalakas et al 14 showed that polymyositis developed in 50% of primates infected with the simian acquired immunodeficiency syn- drome virus. The simian virus was isolated from muscle tissue homoge- nates in these primates. In humans, the presence of HIV has been detect- ed by polymerase chain reaction in skeletal muscle. 15 Other researchers have postulated that HIV infection causes an immunogenic response that leads to the invasion of muscle by inflammatory elements. 13 The demonstration of a mononuclear cell infiltrate that includes CD4 and CD8 T lymphocytes in involved muscle supports this hypothesis. A third theory is that an underlying op- portunistic infection causes chronic antigenic stimulation and a reactive response in muscle tissue. 16 The diagnosis of polymyositis is made both on the clinical presenta- tion of progressive hip and shoulder girdle weakness and on the data from objective studies, such as MRI, electromyogram (EMG), and muscle biopsy. Because the inflammatory process is isointense relative to mus- cle, it may be difficult to discern on T1-weighted MRI. However, in- creased signal intensity can be de- tected on T2-weighted images. Un- like pyomyositis, rim enhancement is not present. Histologic examina- tion shows extensive perivascular and interstitial lymphocytic infiltra- tion, necrosis, and phagocytosis of degenerated muscle tissue. EMG studies demonstrate myopathic pat- terns characterized by short dura- tion, low amplitude, and polyphasic potentials. Fibrillation potentials at rest are seen occasionally. 13 Results of nerve conduction studies are nor- mal. Treatment with anti-inflammatory agents, including oral prednisone, has been extremely effective. Al- though the use of systemic steroids in an immunocompromised patient must be carefully weighed, the use of prednisone at doses of up to 60 mg/day does not seem to cause worsening of the HIV infection or faster progression to AIDS. 13 AZT Myopathy Long-term treatment with AZT can induce a reversible toxic mito- chondrial myopathy that mimics polymyositis clinically. AZT myop- athy is usually dose-related and has been reported in as many as 17% of patients on chronic AZT therapy. 16 Patients usually present with myal- gia, fatigue, proximal muscle weak- ness, and elevated serum CK levels. Myopathic changes are evident on EMG studies. Patients improve with discontinuation of the medication, and both the serum CK and EMG measures subsequently normalize. AZT myopathy is considered multi- factorial and may involve nutritional deficiencies. 16 Discontinuation of AZT and alternative antiviral ther- apy is recommended for patients with AZT myopathy. The ability of AZT to induce myopathy in nonin- fected individuals or to cause toxicity in muscle cell cultures has not been demonstrated. A B Figure 2 An HIV-infected patient with pyomyositis (Staphylococcus aureus) of his thigh. A, Axial T1-weighted MRI scan demonstrates low-intensity signal (arrow) in adductor muscles and adjacent ischium. B, T2-weighted MRI scan in the same patient demonstrates high signal intensity (arrow) in the adductor muscles and ischium. Ayaz A. Biviji, MD, et al Vol 10, No 5, September/October 2002 315 Skeletal Infections Tuberculosis Osteomyelitis The HIV epidemic has led to a resurgence of tuberculosis and is a serious setback in the war against this Mycobacterium infection. 17 Until 1985, the incidence of tuberculosis steadily declined in industrialized countries. Recent increases in tuber- culosis cases in the United States are directly attributable to the rising number of patients immunocom- promised by HIV infection. The prevalence of tuberculosis is 500 times greater in HIV-infected per- sons than in the non–HIV-infected population. 17 This increased sus- ceptibility is caused by a depletion and functional impairment of CD4 lymphocytes, macrophages, and monocytes. These patients are also at increased risk of latent tuberculo- sis reactivation and extrapulmonary disease, including tuberculosis osteomyelitis (Fig. 3). M tuberculosis is a common pathogen in HIV- infected individuals who have mus- culoskeletal infections. In some regions of Africa, one third of adults are HIV positive, and tuberculosis infections have radically changed orthopaedic practice. Orthopaedic surgeons in North America and Europe now must reacquaint them- selves with treating these infections. Tuberculosis osteomyelitis devel- ops from a hematogenous seeding of M tuberculosis from a newly acquired or reactivated pulmonary infection. Of 188 consecutive tuber- culosis patients treated at the Uni- versity of Zambia, the spine was in- volved in 66%, the hip in 18%, the knee in 10%, other joints in 5%, and other bones in 1%. 18 The thoracic and lumbar (especially L1) regions are most commonly affected; in- volvement of the cervical spine or sacrum is atypical. In contrast to bacterial infections, tuberculosis starts in the vertebral body and spreads to adjacent disk spaces. 19 The infection usually begins in the anterior portion of the vertebral body and may spread underneath the anterior longitudinal ligament and extend into the soft tissues. Soft-tissue extension in the lumbar spine may lead to a psoas abscess with the characteristic calcifications that are a distinguishing feature of tuberculosis. In other bones, the metaphyseal region is most com- monly involved, sometimes leading to joint sepsis. Tuberculosis can be differentiated from bacterial infections on plain radiographs by the presence of cal- cified (cold) soft-tissue abscesses and late disk involvement relative to the vertebral body in the spine. MRI findings are similar to those of bacterial osteomyelitis, with low signal on T1-weighted images and high signal on T2-weighted images. In the thoracic spine, the infection may extend posteriorly into the epidural space and cause cord com- pression. Treatment consists pri- marily of chemotherapy, with surgi- cal débridement and stabilization procedures reserved for refractory cases, progressive neurologic deficit, or structural instability. The dura- tion of antibiotic tuberculosis thera- py usually is longer in HIV-infected patients than in immunocompetent patients, with standard treatments often lasting longer than 1 year. Bacillary Angiomatosis Bacillary angiomatosis is a unique multisystem infection caused by the gram-negative rod Bartonella henselae (formerly Rochalimaea henselae) that is seen exclusively in immunocom- promised patients. Epidemiologic data suggest that both a cat bite and cat scratch are strong risk factors. Distinct vascular proliferations of skin, viscera, and lymph nodes usu- ally are seen in this infectious process. Multiorgan involvement may include adenitis, intracerebral mass lesions, aseptic meningitis, peliosis hepatis, and osteomyelitis. Cutaneous lesions are characterized by friable angiomatous papules, which may be difficult to distinguish from Kaposi’s sarcoma lesions. The presence of osseous lesions, which are not typically seen with Kaposi’s sarcoma, may help differentiate this disease. One third of patients with bacillary angiomatosis have osseous lesions, which are lytic and can be associated with periostitis and a soft-tissue mass 20 (Fig. 4). Extensive cortical damage and medullary per- meation are seen on radiographs, often preceding the cutaneous le- sions by many months. The overly- ing skin changes may resemble cel- lulitis. There is usually an increased uptake on technetium 99m bone scan, and MRI shows the nonspecific changes of osteomyelitis. Warthin- Starry silver staining is used to iden- tify the bacillary organism. Because bacillary angiomatous osteomyelitis can be successfully treated with eryth- romycin, biopsy and early institution of therapy are recommended in any HIV-infected patient presenting with an osteolytic lesion. Such lesions Figure 3 An HIV-infected patient with tuberculosis osteomyelitis of the right hand and wrist. Anteroposterior radiograph of the hand shows extensive destructive changes of the carpus with periosteal reac- tion of the adjacent metacarpals. Musculoskeletal Manifestations of HIV Infection Journal of the American Academy of Orthopaedic Surgeons 316 have been shown to regress with anti- biotics. If left undiagnosed and un- treated, bacillary angiomatosis may be fatal, with patients succumbing to overwhelming infection with the involvement of many internal organs. Neoplastic Conditions Non-Hodgkin’s Lymphoma The first reports of non-Hodg- kin’s lymphoma in patients with AIDS appeared in 1982. It is the sec- ond most common type of tumor in HIV-infected persons after Kaposi’s sarcoma and is 60 times more preva- lent relative to the general popula- tion. 21 Non-Hodgkin’s lymphoma tends to be more aggressive in HIV- infected individuals, with presenta- tion at more advanced stages, and it is one of the diagnostic criteria for AIDS. Casado et al 7 found that HIV- positive patients with bone lym- phoma had a mean CD4 count of 130 cells/mm 3 . Extranodal involve- ment, including the central nervous system, bone marrow, abdominal organs, and mucocutaneous sites, is frequently seen. Lymphomatous in- filtration of muscle may be difficult to differentiate from pyomyositis. Primary and secondary bone involvement is reported in 20% to 30% of cases and predominantly affects the lower extremities. 21 Pa- tients may present with pain, fever, weight loss, and a pathologic frac- ture. On plain radiographs, the lesion usually appears osteolytic, with cortical destruction that can have a permeative pattern. Other features include purely sclerotic lesions or mixed sclerotic and osteo- lytic lesions with an indistinct zone of transition. Periosteal reaction with an associated soft-tissue mass also may be seen. MRI can show the extent of bone marrow involve- ment, which typically has a low sig- nal appearance on T1-weighted images and a high signal appear- ance on T2-weighted images. Bac- terial osteomyelitis also may have the same appearance on imaging studies and must be considered in the differential diagnosis. Biopsy definitively confirms diagnosis, and treatment includes chemotherapy and radiation, with surgical debulk- ing in selected cases. Kaposi’s Sarcoma An unusual clustering of cases of Kaposi’s sarcoma reported in 1982 led to the discovery of HIV. This multifocal neoplasm arises from lymphatic endothelial cells and may progress to tumorous masses. Approximately 20% of AIDS pa- tients eventually develop Kaposi’s sarcoma. 1 Osseous involvement, al- though rare, is seen more frequently with the endemic African type of Kaposi’s sarcoma. In a Ugandan study, 22 10 of 16 patients with florid Kaposi’s sarcoma had bone lesions ranging from discrete erosions to diffuse osteopenia on plain radio- graphs. Cortical destruction directly beneath the cutaneous tumors was observed in 13 of these patients. Treatment consists of chemotherapy and radiation. Inflammatory Arthropathies Knowledge of rheumatic manifesta- tions of HIV continues to evolve. In 1985, the National Institute of Arthritis and Musculoskeletal and Skin Disease began to investigate the rheumatic complications of HIV. Several authors have suggested a possible co-occurrence of Reiter’s syndrome and other reactive arthrit- ides with HIV because of the higher prevalence of the conditions in HIV- infected persons. 23 A similar ob- servation has been made in Africa, where reactive arthritides, which are usually related to outbreaks of dys- entery during the rainy season, also have become more frequent since the outbreak of the HIV epidemic. 18 These arthropathies are more severe and respond poorly to standard therapies in HIV-positive individu- als. Interestingly, immune-mediated rheumatic conditions, such as sys- temic lupus erythematosus and rheumatoid arthritis, improve as the immune system deteriorates. 1,24 One third of HIV-infected patients experience arthralgias during the course of their disease, and it may be the first manifestation of HIV for some patients. 2 Several arthropa- thies, such as Reiter’s syndrome, psoriatic arthritis, HIV-associated arthritis, painful articular syndrome, acute symmetric polyarthritis, and hypertrophic osteoarthropathy, are either more prevalent in or distinctly unique to the HIV-infected popula- tion. The spectrum of presentations ranges from mild arthralgia to severe joint disability. The etiology and pathogenesis of these arthropa- thies are controversial and poorly understood. These conditions may even simulate septic arthritis, mak- ing their diagnosis and management even more challenging. Reiter’s Syndrome Reiter’s syndrome is 100 to 200 times more frequent in the HIV- infected population than in the non- infected, with a prevalence rate of 5% to 10%. 25 In 1987, Winchester et al 23 described a group of 13 patients with HIV and Reiter’s syndrome. In Figure 4 An HIV-infected patient with bacillary angiomatosis. Lateral radiograph of the radius shows a lytic lesion of the cor- tex (asterisk) with an associated periostitis. * Ayaz A. Biviji, MD, et al Vol 10, No 5, September/October 2002 317 this series, the pattern of joint in- volvement tended to be oligoarticu- lar, with a predisposition for the lower extremities. Nine patients were HLA-B27 antigen positive. Enthesopathic manifestations, pre- dominantly Achilles tendinitis, were noted in 11 of the patients and were described as painful and incapaci- tating. Reiter’s syndrome is remarkable for its severity in HIV-positive patients. The debilitating clinical course is usually refractory to non- steroidal anti-inflammatory drugs (NSAIDs). The classic triad of ure- thritis, conjunctivitis, and seronega- tive arthritis may be observed, as well as asymmetric oligoarthritis that mainly affects the large joints in the lower extremity. Presentation in the foot includes an enthesopathy, which frequently involves the Achil- les tendon, plantar fascia, and exten- sor tendons, as well as anterior and posterior tibial tendons. Clinically this may be termed AIDS foot, which presents as a broad-based gait with weight bearing through the lat- eral margins of the feet to protect the painful heel. It can be extremely dis- abling, forcing some patients to be wheelchair bound, and may mimic a peripheral neuropathy. Upper ex- tremity enthesopathy may include medial or lateral epicondylitis, rota- tor cuff tendinitis, de Quervain’s tenosynovitis, or flexor tendinitis. Axial skeleton involvement is rare. Osteopenia and erosion at tendi- nous insertion sites (eg, Achilles tendon and plantar fascia) are often seen. The erythrocyte sedimenta- tion rate and C-reactive protein level are usually elevated, and syn- ovial fluid analysis reveals a white blood cell count in the range of 27,000 to 50,000/mm 3 . The etiology of Reiter’s syndrome is unclear. HLA-B27 antigen is pres- ent in approximately 70% to 80% of affected patients, compared with 6% to 10% in the general population. 23 Many investigators have concluded that either an enteric or venereal in- fection is the environmental link in the pathogenesis of Reiter’s syn- drome. Winchester et al 25 reported that 4 of the 13 patients in their series had an antecedent enteric infection with either Shigella flexneri or Campylobacter jejuni. Eleven of the 13 patients had a diarrheal illness that preceded the arthritis. Enteric Yersinia infection also has been re- ported in the development of Reiter’s syndrome. A growing body of liter- ature supports the theory that a mo- lecular mimicry between MHC class I antigens and the infecting bacteria in an HLA-B27–positive host trig- gers these arthropathies. The im- mune system essentially is tricked into attacking tissue containing HLA- B27 antigen as well as the offending organism. Amino acid sequences shared with HLA-B27 have been demonstrated for Klebsiella pneumo- niae and S flexneri. HIV-infected patients are more susceptible to these enteric infections, which also include Giardia lamblia and Chlamydia tra- chomatis. This heightened suscepti- bility may account for the higher prevalence of these arthropathies in the HIV-infected population. The management of Reiter’s syn- drome is often difficult. Although NSAIDs are often ineffective, sec- ond-line agents such as phenylbuta- zone and sulfasalazine have been shown to be more effective. 3 Immu- nosuppressive agents, including cyclosporine and prednisone, have been used successfully in patients with symptoms refractory to initial treatments. However, the use of methotrexate is contraindicated. Full-blown AIDS and Kaposi’s sar- coma may develop after methotrex- ate treatment. 23 Psoriatic Arthritis Psoriatic arthritis is 10 to 40 times more frequent in the HIV-infected population than in the general pop- ulation, with a reported prevalence between 2% and 3%. 26 These pa- tients have severe cutaneous disease, with the development of arthritis preceding an accelerated progres- sion to full-blown AIDS. Psoriatic arthritis may be clinically difficult to differentiate from Reiter’s syn- drome. In one report, 26 the arthritis preceded the psoriasis in 16% of patients, making the diagnosis even more challenging. Typical cuta- neous manifestations include cir- cumscribed, discrete, and confluent red, silvery scaled maculopapules that occur predominantly on the elbow, knee, scalp, and trunk. Nail changes can range from pitting to severe destruction. Five patterns have been described: asymmetric oligoarthritis, symmetric polyarthri- tis, dominant desquamative intersti- tial pneumonia, arthritis mutilans, and sacroiliitis or spondylitis with- out peripheral involvement. 26 Syno- vial white blood cells typically range between 7,000 and 15,000/mm 3 . Radiologic findings include marginal erosion, soft-tissue swelling, osteo- penia, osteolysis, and so-called pen- cil-in-cup deformities in the digits. Like Reiter’s syndrome, the patho- genesis of psoriatic arthritis may be related to the combination of a genetic predisposition and an arthri- togenic infection. Management of psoriatic arthritis is similar to that for Reiter’s syndrome. HIV-Associated Arthritis HIV-associated arthritis, a sub- acute oligoarthritis, was first de- scribed by Rynes et al 24 in 1988 and is unique to HIV-infected patients. Symptoms typically develop over 1 to 6 weeks and may last up to 6 months. Characteristic features in- clude exquisite, incapacitating joint pain, predominantly in the knee and ankle. Synovial fluid analysis reveals a noninflammatory reaction with a white blood cell count in the range of 50 to 2,600/mm 3 . Radio- graphic findings are typically unre- markable, although osteopenia may be evident from disuse or chronic Musculoskeletal Manifestations of HIV Infection Journal of the American Academy of Orthopaedic Surgeons 318 synovitis. Synovial biopsy shows a chronic process with a predominantly mononuclear cell infiltrate. Proposed etiologies include a reactive mechanism to deposited immune complexes or direct HIV infection of the synovium. The latter theory has been supported by a pos- itive culture assay for HIV in the synovial fluid of a patient with this condition. 27 Neither rheumatoid factor nor HLA-B27 antigen are associated with this particular arthri- tis, which may help distinguish it from other arthropathies. Intra- articular steroid injections have proved to be an extremely effective, safe, and rapid treatment, and no cases of secondary infections have been reported. HIV infection should be considered with any sus- picion of bacterial or mycobacterial arthritis. Painful Articular Syndrome Painful articular syndrome is seen in as many as 10% of patients with AIDS. 24 The hallmark of this arthritis is a sharp, severe arthralgia of acute onset that often simulates a septic joint. Emergency room care or hospitalization is required in more than half of cases. 2 The knee is most commonly affected, but the elbow and shoulders also can be involved. This condition can be dis- tinguished from a septic joint by its intermittent pain pattern and lack of effusion or synovitis on physical examination. Joint aspiration re- veals no inflammatory fluid and a normal percentage of polymor- phonucleocytes. This self-limited condition lasts from 2 to 24 hours and responds well to narcotics and anti-inflammatory medications. Ra- diographic features are nonspecific, with occasional periarticular osteo- penia seen. The mechanism for this unique arthritis is speculative; current theories include cytokine elaboration and a transient bony ischemia. Management is expectant with analgesic medications. Acute Symmetric Polyarthritis Acute symmetric polyarthritis is unique to HIV-infected patients and resembles rheumatoid arthritis both clinically and radiographically. Small joint involvement in the hand is common, and characteristic fea- tures include ulnar deviation and swan neck deformities. This rare condition differs from rheumatoid arthritis by its acute onset and the fre- quent presence of negative rheuma- toid factor. Periarticular osteopenia, joint space narrowing, and marginal erosion are seen on radiographs. Unlike rheumatoid arthritis, prolifer- ative changes also may be observed. Gold has been used successfully as treatment. 24 Hypertrophic Osteoarthropathy Hypertrophic osteoarthropathy is a systemic disorder seen with pul- monary neoplasms and pyogenic infections (eg, empyema and lung abscesses) and can affect bones, joints, and soft tissues. In HIV- infected patients with Pneumocystis carinii pneumonia, this condition re- solves with treatment of the pneu- monia. 28 Severe pain in the lower extremity is typical, and clinical manifestations include arthralgias, nonpitting edema, digital clubbing, and periarticular soft-tissue involve- ment of the ankle, knee, and elbow. Neurovascular changes of the hand and foot, such as chronic erythema, paresthesias, and increased sweat- ing, can be observed. The skin over affected areas often has a glis- tening appearance and may feel warm and edematous. Extensive periosteal reaction and subpe- riosteal proliferative changes of the long bones in the lower extremity are seen on plain radiographs. Bone scan reveals increased uptake along cortical surfaces. Treatment is directed at the underlying pneu- monia. Surgical or chemical vago- tomy or radiation therapy has been used to relieve bone pain in refrac- tory cases. Figure 5 A 34-year-old HIV-infected person developed bilateral hip pain 21 months after initiation of protease inhibitor treatment. Anteroposterior pelvic radiograph demonstrates subchondral lucency and collapse in the superior portion of the right femoral head and patchy sclerosis of the left femoral head. These radiographic changes are consistent with osteonecrosis of both femoral heads. Ayaz A. Biviji, MD, et al Vol 10, No 5, September/October 2002 319 Osteonecrosis An increasing number of cases of osteonecrosis of the femoral head in the HIV-positive population have been reported recently, 29 and a direct link between HIV and osteonecrosis has been proposed. 30 Embolic phe- nomena secondary to the formation of antiphospholipid antibodies and immune complexes, protein S defi- ciency, and hypergammaglobulin- emia also have been proposed as eti- ologies. Our series at the University of California, San Francisco demon- strated a strong association between chronic protease inhibitor use and the development of osteonecrosis in HIV-infected patients 30 (Figs. 5 and 6). Lipid metabolism disturbances secondary to protease inhibitors that result in hyperlipidemic states and an associated lipodystrophy syn- drome have been described. 31 These systemic effects may explain the rela- tionship between protease inhibitor use and osteonecrosis of the femoral head. Osteonecrosis should be con- sidered in the differential diagnosis in HIV-infected patients with hip pain. A higher vigilance for osteo- necrosis is especially crucial for pa- tients taking protease inhibitors. Surgical Outcomes In urban centers, 3% to 7% of ortho- paedic patients who receive emer- gent care and 1% to 3% who undergo elective procedures are HIV posi- tive. 32 Complications of greatest concern include impaired bone and soft-tissue healing as well as postop- erative infections. Of HIV-infected hemophiliac patients undergoing elective arthroplasty and non- arthroplasty procedures, asympto- matic individuals with CD4 counts >200 cells/mm 3 are not at higher risk of postoperative infection than the general population. 33 In the trauma setting, however, asympto- matic HIV-infected patients may be at increased risk. Paiement et al 34 reported a fivefold increase in risk of infection in HIV-infected patients after open fractures. A longer dura- tion of prophylactic parenteral anti- biotics may be required in this subset of patients. Careful preoperative evaluation, including assessment of the nutritional and immune status of these patients, should be done before elective orthopaedic surgery. Routine HIV testing is a contro- versial issue. It is not clear whether there is any benefit to routine HIV testing of trauma patients or elective patients, either for the individual patient or because of concerns for public health. Guidelines from national professional organizations, where they do exist, are not very specific. Principal consideration for HIV testing is whether it is of bene- fit to the patient, which is a basic tenet of ethical practice. Trauma and elective patients are not screened routinely at our institution and we do not recommend it. Summary Musculoskeletal manifestations of HIV infection are frequent and involve muscle, bone, and joints. The disease processes can be inflam- matory, infectious, or neoplastic and often are unique to the HIV infec- tion itself or to the immunocompro- mising nature of this progressive condition. Disease processes can be either a direct consequence of the virus and circulating immune com- plexes or secondary to the oppor- tunistic infections that occur in HIV- infected persons. Patients often pre- sent as a diagnostic and treatment challenge. The treating orthopaedic surgeon must take into considera- tion the myriad of debilitating man- ifestations of the disease and its treatment to effectively manage this unique group of patients. Espe- cially for the orthopaedic surgeon who does not routinely treat HIV- positive patients, a multidiscipli- nary approach is strongly recom- mended, including a rheumatolo- gist, physical therapist, neurologist, infectious diseases specialist, pain consultant, musculoskeletal radiolo- gist, and the patient’s primary physician. 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