CURRENT CONCEPTS REVIEW- HIV and ORTHOPAEDICS

Dr. Libin Thomas Manathara

A Journal Club presentation at

Amala Institute of Medical Sciences, Thrissur

Introduction

• A larger number of HIV-positive patients may present for elective andemergency surgery as modern antiretroviral treatment has increasedlife expectancy and quality of life

• A young person with promptly recognized and treated HIV infectionshould now have a life expectancy very similar to that of age-matched, uninfected individuals

Topics

• Musculoskeletal Manifestations

• Outcomes in Orthopaedic Surgery

Musculoskeletal Manifestations

• Bone Disorders

• Osteomyelitis

• Osteonecrosis

• Joint Disease

• Septic Arthritis

• Other arthropathies

• Myopathies

• Infectious Pyomyositis

• Primary and/or Noninfectious Myositis

• Neoplasms

• Kaposi Sarcoma

• Non-Hodgkin Lymphoma

Bone disorders- Osteomyelitis

• 13% of cases of tuberculosis are associated with HIV

• The spine is the most common site of involvement

• Because of the relative lack of proteolytic enzymes, tuberculosis has a tendency to spare theintervertebral disc, spreading in a subligamentous fashion in the anterior soft tissues, andresulting in partially calcified “cold abscesses” that show little evidence of active inflammation

• In HIV-positive patients, there is a trend toward• larger epidural abscesses• less vertebral body collapse• subsequent kyphosiscompared with endemic tuberculous spondylitis

• Among nontuberculous osteomyelitis, Staphylococcus represents the most commoncause in adults with HIV

• Other causes of osteomyelitis in HIV-infected patients include secondary syphilis andbacillary angiomatosis caused by Bartonella henselae

Bone disorders- Osteonecrosis

• Osteonecrosis may be directly mediated by the HIV virus or may be secondary toembolic phenomena because of antiphospholipid antibody formation, protein Sdeficiency, and hypergammaglobulinemia

• Magnetic resonance imaging (MRI) has a sensitivity of 99% and is the imagingmodality of choice for diagnosis and staging

• There is no effective treatment to arrest, delay, or reverse the progression ofsubchondral collapse and bone destruction, and surgery is often required

Joint disease- Septic Arthritis

• Arthropathy commonly arises from both pyogenic and atypical organisms

• Older literature had suggested that opportunistic infections accounted for amajority of the cases of septic arthritis in HIV patients; however, morerecently, authors have maintained that Staphylococcus aureus remains themost common pathogen in septic arthritis regardless of HIV status

• A high index of suspicion of opportunistic organisms in septic arthritis isrequired when patients present with a CD4 count of <200/mm

• The Phemister triad, consisting of• peripheral erosions• juxtaarticular osteopenia• gradual joint-space loss,has been classically associated with mycobacterial arthropathy

Joint disease- Other arthropathies

• Primary HIV arthropathy is a transient (duration of <6 weeks), non erosive,oligoarthritis preferentially affecting the lower extremities

• Seronegative spondyloarthropathies such as psoriatic arthritis and reactivearthritis are 40 to 200 times more common in HIV-infected patients- here diseasecourse is frequently more debilitating in the setting of HIV than in non infectedpatients

Myopathies- Infectious Pyomyositis

• Bacterial myositis (pyomyositis) is one of the more common late complicationsof HIV to affect the musculoskeletal system

• The most frequently implicated organism is S. aureus• Pyomyositis is very often an indicator of late-stage with CD4 counts typically

of <200 cells/mm• There are 3 stages of pyomyositis that describe increasing disease severity:

invasive, suppurative, and late• The serum creatinine kinase level, as opposed to the erythrocyte

sedimentation rate (ESR), is generally not elevated, in contradistinction topolymyositis and rhabdomyolys

• Early recognition and aggressive management with parenteral antibiotics andsurgical drainage are mainstays of treatment

Myopathies- Primary and/or Noninfectious Myositis• Primary HIV infection can result in nonbacterial myositis and rhabdomyolysis

• Patients typically present with proximal muscle weakness that is relatively symmetric

• This entity should be a diagnosis of exclusion after a meticulous search for infectiousetiologies, including fungal, atypical mycobacterial, and other unusual organisms, hasbeen conducted

• MRI may aid in the identification of an optimal target from which to obtain tissue forculture and biopsy

• Histologic examination shows extensive perivascular and interstitial lymphocyticinfiltration, necrosis, and phagocytosis of degenerated muscle tissue

• Seroconversion may present with influenza-like clinical features including myalgia, whichcan be associated with MRI findings identical to those of polymyositis

• In fact, bilateral proximal muscle weakness and elevated serum creatinine kinasepresenting in high-risk individuals may justify screening for HIV

Neoplasms- Kaposi Sarcoma

• Kaposi sarcoma is an angioproliferative neoplasm, associated withhuman herpesvirus 8, that is likely of lymphatic origin; typically involvesthe skin, mucosa, and lymphatics; and, once the CD4 count decreases to<200cells/mm3, appears as a late complication

• Kaposi sarcoma only rarely involves the musculoskeletal system, andusually does so secondary to contiguous extension from mucocutaneousinvolvement; however, there are case reports of metastaticdissemination

• Most osseous lesions are osteolytic and destructive, although scleroticand expansile lesions are occasionally seen

• Treatment consists of chemotherapy and radiation

Neoplasms- Non-Hodgkin Lymphoma

• Non-Hodgkin lymphoma risk in HIV-positive patients is approximately 60 timesthat in the general population

• Patients may present with painful limb swelling, pathological fracture and B-typeconstitutional symptoms

• However, Santos et al. showed that, in AIDS patients with fevers of unknownorigin, bone marrow biopsy rarely resulted in the diagnosis of non-Hodgkinlymphoma

• Skeletal involvement can be observed in up to 20% to 30% of patients and lesionsare typically osteolytic and commonly associated with a soft-tissue mass

• Because of the rapid tumor growth rate, periosteal reaction is frequently absent

• Anthracycline-based chemotherapy and radiation therapy (30to 40 Gy) shouldfollow as adjuvant treatment for consolidation and durable complete remission

• The 5-year overall survival is 5% to 10%

Outcomes in Orthopaedic Surgery

• Joint Replacements (Total Knee and Total Hip Arthroplasty)

• Hip Arthroplasty

• Knee Arthroplasty

• Orthopaedic Trauma• Early Infection Rates

• Bone Union

• Late Infection

• Polytrauma

Hip Arthroplasty

• Lin et al demonstrated that HIV-positive patients are more likely thanHIV-negative patients to develop acute renal failure, a woundinfection and undergo postoperative irrigation and debridement

• However, HIV-positive patients were less likely to have a myocardialinfarction, and the overall complication rates were similar betweenindividuals with and without HIV infection

• Naziri et al found that HIV-positive patients compared with patientswho did not have HIV had an increased risk of major and minorperioperative complications

Knee Arthroplasty

• Boylan et al found that people with HIV who had a total kneearthroplasty had an increased risk of perioperative wound infectionsand a longer length of stay but no increased adjusted risk of overallcomplications

Cofactors

• Hemophilia: The deep infection rate is increased in HIV-positive patients withhemophilia who have a revision

• CD4 counts: Patients with CD4 counts of <200 cells/mm3 had a tenfold increasedrisk of infection

• Intravenous drug users: Patients who are intravenous drug users have anincreased deep infection rate and risk of total hip replacement failure

• cART: Treatment with cART may offer little or no overall difference in infectionrates, postoperative complications, clinical outcomes, or implant failure, on thebasis of the findings of nonrandomized controlled trials

Orthopaedic Trauma

• Low bone mineral density (BMD) and decreased bone mass affect HIV-infectedpatients independently of age and sex

• HIV can generate the release of inflammatory cytokines that may promoteosteolysis and bone resorption

• Moreover, high concentrations of HIV RNA increases osteoclast presence in bone

• Particular concerns in treating fractures in HIV-positive patients include early andlate wound infection rates, bone union, and polytrauma

Early Infection Rates

• Older literature has suggested that HIV-positive patients with internal fixation of fractures had anincreased risk of infection but the use of cART has changed these findings

• Harrison et al used the ASEPSIS scoring system (Additional treatment, the presence of Serousdischarge, Erythema, Purulent exudate, and Separation of the deep tissues, the Isolation ofbacteria, and the duration of inpatient Stay) to assess wounds and found an infection rate of onlya 3.5% among HIV-positive patients which was comparable with that in the HIV negative group(5%)

• When open fractures are involved, an increase in the infection rates can be expected

• Bates et al. found a slightly higher infection rates for open or contaminated fractures in HIV-positive patients

• There is still controversy in this area

• External fixators are widely used for treating open fractures, but an increased pin-track infectionrate within HIV-positive patients has not been confirmed

Bone Union

• There are a number of issues that complicate the study of the effect of the HIVstatus on the outcome of fracture-healing

• The unraveling of the effect of HIV infection from those of immune reconstitutionafter cART, drug side effects, cachexia, and secondary infections demandsrigorous study designs, and for these reasons there is still controversy on thistopic

• It is well recognized that fracture-healing is initiated by an inflammatory responseto bone injury

• Although HIV infection is immunosuppressive, there are increased serum levels ofTNF-a, which in noninfected individuals would contribute to the formation ofcallus and bone repair; however, an increased baseline level could lead todesensitization, preventing or decelerating the healing process

Bone Union

• Harrison et al. found an increase in the incidence of nonunion of externallystabilized tibial fractures in HIV-positive patients compared with HIV-negativepatients, although the difference was not significant

• The same authors, in a later prospective study of open tibial fractures did not findany difference between patients with and without HIV with respect to fractureunion at 6 months

• As we can see, there is no correlation between clinical results and the theoreticalhypothesis mentioned above, i.e., that increased baseline levels of TNF-a couldlead to desensitization, preventing or decelerating the healing process; however,this could be related to confounding bias when designing the studies andwarrants further investigation

Late Infection

• There is a theoretical risk of late infection around implants in patientswith HIV; however, this has not been proven in the clinical setting

• At this point, there is no indication to routinely remove implants afterfracture union

Polytrauma

• There is no difference in the mortality rate after polytrauma for HIV-positivepatients compared with HIV-negative patients

• But HIV-positive patients carry a higher risk of pulmonary, renal, and infectious orseptic complications

• Also, no difference has been found with respect to the length of stay in theintensive care unit

• However, HIV-positive patients have a substantially longer hospital stay, probablybecause of the complications that they develop

• The rates of early and late infection around implants in HIV-positive patients arecomparable with those in the HIV negative population HIV-infected individualshave been shown to have a twofold to tenfold increased risk of venousthrombosis, which has to be taken into account when treating this population

Overview

• Advances in cART in recent years have transformed HIV infection into achronic disease when treatment is available, increasing a patient’s lifeexpectancy and the chances that an orthopaedic surgeon will treatpatients within this population

• These patients can be affected by musculoskeletal conditions andneoplasms that are usually not seen in immunocompetent individuals

Overview

• Furthermore, as life expectancy increases, HIV-positive patients aremore susceptible to age-related pathology such as osteoarthritis thatmay require surgical intervention

• Since the advent of cART, total joint arthroplasty has been shown tobe a safe procedure; however, perioperative infection remains a smallrisk in patients with uncontrolled viral loads or CD4 counts of <400cells/mm3

Overview

• With regard to trauma surgery, the rates of early and late infectionaround implants, as well as union rates, are comparable with those inthe HIV-negative population; however, there is an increased risk ofpulmonary, renal, and infectious or septic complications in thepolytrauma setting

• Factors such as CD4 count, nutritional status, cART, viral load count,and other comorbidities (hemophilia, intravenous drug use, etc.)should be considered when treating these patients in order tooptimize their outcomes

Overview

• Even though there are several studies dealing with this topic, weshould be aware of the limitations within this field such as the lack ofrandomized trials involving HIV-infected patients and the missing datarelated to CD4 count, viral load, nutritional status, and renal conditionin the perioperative period within some of these studies

• Future studies should take into account these limitations and shouldrecord the details with regard to these factors since the use of cART isnow a more common treatment

Thank You