osteoarthritis

5/4/2014 Osteoarthritis

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Osteoarthritis Author: Carlos J Lozada, MD; Chief Editor: Herbert S Diamond, MD more...

Updated: Apr 3, 2014

Practice EssentialsOsteoarthritis is the most common type of joint disease, affecting more than 20 million individuals in the UnitedStates alone. It can be thought of as a degenerative disorder arising from the biochemical breakdown of articular(hyaline) cartilage in the synovial joints. However, the current view holds that osteoarthritis involves not only thearticular cartilage but also the entire joint organ, including the subchondral bone and synovium.

Essential update: Study identifies the most effective physical therapy programs for kneeosteoarthritis

In a systematic review and metaanalysis of 48 randomized controlled trials, Juhl and colleagues found that theoptimal exercise program for reducing pain and patientreported disability in knee osteoarthritis should have asingle aim, which can be improving aerobic capacity, strengthening the quadriceps muscle, or improving lowerextremity performance. For best results, the exercise program should be supervised and performed 3 timesweekly.[1]

Signs and symptoms

Symptoms of osteoarthritis include the following:

Deep, achy joint pain exacerbated by extensive use The disease’s primary symptomReduced range of motion and crepitus Frequently presentStiffness during rest (gelling) May develop, with morning joint stiffness usually lasting for less than 30minutes

Osteoarthritis of the hand

Distal interphalangeal (DIP) joints are most often affectedProximal interphalangeal (PIP) joints and the joints at the base of the thumb are also typically involvedHeberden nodes, which represent palpable osteophytes in the DIP joints, are more characteristic in womenthan in menInflammatory changes are typically absent or at least not pronounced

See Clinical Presentation for more detail.

Diagnosis

Osteoarthritis is typically diagnosed on the basis of clinical and radiographic evidence.[2, 3, 4, 5, 6] No specificlaboratory abnormalities are associated with osteoarthritis.

Imaging studies

Plain radiography The imaging method of choice because radiographs are costeffective and can bereadily and quickly obtained[4, 7] ; in the loadbearing areas, radiographs can depict jointspace loss, as wellas subchondral bony sclerosis and cyst formationComputed tomography (CT) scanning Rarely used in the diagnosis of primary osteoarthritis; however, itmay be used in the diagnosis of malalignment of the patellofemoral joint or of the foot and ankle jointsMagnetic resonance imaging (MRI) Not necessary in most patients with osteoarthritis unless additionalpathology amenable to surgical repair is suspected; unlike radiography, MRI can directly visualize articularcartilage and other joint tissues (eg, meniscus, tendon, muscle, or effusion)Ultrasonography No role in the routine clinical assessment of patients with osteoarthritis; however, it isbeing investigated as a tool for monitoring cartilage degeneration, and it can be used for guided injections

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of joints not easily accessed without imagingBone scanning May be helpful in the early diagnosis of osteoarthritis of the hand[8] ; bone scans also canhelp differentiate osteoarthritis from osteomyelitis and bone metastases

Arthrocentesis

The presence of noninflammatory joint fluid helps distinguish osteoarthritis from other causes of joint pain. Othersynovial fluid findings that aid in the differentiation of osteoarthritis from other conditions are negative Gram stainsand cultures, as well as the absence of crystals when fluid is viewed under a polarized microscope.

See Workup for more detail.

Management

Nonpharmacologic interventions

The cornerstones of osteoarthritis therapy, nonpharmacologic interventions include the following:

Patient educationHeat and coldWeight loss[9]ExercisePhysical therapyOccupational therapyUnloading in certain joints (eg, knee and hip)

Pharmacologic therapy

For hand osteoarthritis, the American College of Rheumatology (ACR) conditionally recommends using one ormore of the following:

Topical capsaicinTopical nonsteroidal antiinflammatory drugs (NSAIDs) Including trolamine salicylateOral NSAIDsTramadol

For knee osteoarthritis, the ACR conditionally recommends using one of the following:

AcetaminophenOral NSAIDsTopical NSAIDsTramadolIntraarticular corticosteroid injections

For hip osteoarthritis, the ACR conditionally recommends using 1 or more of the following for initial management:

AcetaminophenOral NSAIDsTramadolIntraarticular corticosteroid injections

Surgery

A referral to an orthopedic surgeon may be necessary if the osteoarthritis fails to respond to a medicalmanagement plan. Surgical procedures for osteoarthritis include the following:

ArthroscopyOsteotomyArthroplasty Particularly with knee or hip osteoarthritisFusion

See Treatment and Medication for more detail.

Image library

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This radiograph demonstrates osteoarthritis of the right hip, including the finding of sclerosis at the superior aspect of the acetabulum.Frequently, osteoarthritis at the hip is a bilateral finding, but it may occur unilaterally in an individual who has a previous history of hiptrauma that was confined to that one side.

BackgroundOsteoarthritis is the most common type of joint disease, affecting more than 20 million individuals in the UnitedStates alone (see Epidemiology). It represents a heterogeneous group of conditions resulting in commonhistopathologic and radiologic changes. It can be thought of as a degenerative disorder arising from biochemicalbreakdown of articular (hyaline) cartilage in the synovial joints. However, the current view holds that osteoarthritisinvolves not only the articular cartilage but also the entire joint organ, including the subchondral bone andsynovium.

Osteoarthritis predominantly involves the weightbearing joints, including the knees, hips, cervical andlumbosacral spine, and feet. Other commonly affected joints include the distal interphalangeal (DIP), proximalinterphalangeal (PIP), and carpometacarpal (CMC) joints. This article primarily focuses on osteoarthritis of thehand, knee, and hip joints (see Pathophysiology). For more information on arthritis in other joints, seeGlenohumeral Arthritis and Wrist Arthritis.

Although osteoarthritis was previously thought to be caused largely by excessive wear and tear, increasingevidence points to the contributions of abnormal mechanics and inflammation. Therefore, the term degenerativejoint disease is no longer appropriate in referring to osteoarthritis. (See Pathophysiology.)

Historically, osteoarthritis has been divided into primary and secondary forms, though this division is somewhatartificial. Secondary osteoarthritis is conceptually easier to understand: It refers to disease of the synovial jointsthat results from some predisposing condition that has adversely altered the joint tissues (eg, trauma to articularcartilage or subchondral bone). Secondary osteoarthritis can occur in relatively young individuals (see Etiology).[10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]

The definition of primary osteoarthritis is more nebulous. Although this form of osteoarthritis is related to the agingprocess and typically occurs in older individuals, it is, in the broadest sense of the term, an idiopathicphenomenon, occurring in previously intact joints and having no apparent initiating factor.

Some clinicians limit the term primary osteoarthritis to the joints of the hands (specifically, the DIP and PIP jointsand the joints at the base of the thumb). Others include the knees, hips, and spine (apophyseal articulations) aswell.

As underlying causes of osteoarthritis are discovered, the term primary, or idiopathic, osteoarthritis may becomeobsolete. For instance, many investigators believe that most cases of primary osteoarthritis of the hip may, infact, be due to subtle or even unrecognizable congenital or developmental defects.

No specific laboratory abnormalities are associated with osteoarthritis. Rather, it is typically diagnosed on thebasis of clinical findings, with or without radiographic studies (see Workup).

The goals of osteoarthritis treatment include pain alleviation and improvement of functional status.Nonpharmacologic interventions are the cornerstones of osteoarthritis therapy and include the following:

Patient educationApplication of heat and coldWeight lossExercisePhysical therapyOccupational therapyJoint unloading, in certain joints (eg, knee and hip)

Intraarticular pharmacologic therapy includes corticosteroid injection and viscosupplementation, which mayprovide pain relief and have an antiinflammatory effect on the affected joint. (See Treatment.) Oral pharmacologic

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therapy begins with acetaminophen for mild or moderate pain without apparent inflammation.

If the clinical response to acetaminophen is not satisfactory or the clinical presentation is inflammatory, considernonsteroidal antiinflammatory drugs (NSAIDs). (See Medication.) If all other modalities are ineffective andosteotomy is not viable, or if a patient cannot perform his or her daily activities despite maximal therapy,arthroplasty is indicated.

The high prevalence of osteoarthritis entails significant costs to society. Direct costs include clinician visits,medications, and surgical intervention. Indirect costs include such items as time lost from work.

Costs associated with osteoarthritis can be particularly significant for elderly persons, who face potential loss ofindependence and who may need help with daily living activities. As the populations of developed nations ageover the coming decades, the need for better understanding of osteoarthritis and for improved therapeuticalternatives will continue to grow. (See Epidemiology.)

AnatomyJoints can be classified in either functional or structural terms. A functional classification, based on movement,would categorize joints as follows:

Synarthroses (immovable)Amphiarthroses (slightly moveable)Diarthroses (freely moveable)

A structural classification would categorize joints as follows:

SynovialFibrousCartilaginous

Normal synovial joints allow a significant amount of motion along their extremely smooth articular surface. Thesejoints are composed of the following:

Articular cartilageSubchondral boneSynovial membraneSynovial fluidJoint capsule

The normal articular surface of synovial joints consists of articular cartilage (composed of chondrocytes)surrounded by an extracellular matrix that includes various macromolecules, most importantly proteoglycans andcollagen. The cartilage facilitates joint function and protects the underlying subchondral bone by distributing largeloads, maintaining low contact stresses, and reducing friction at the joint.

Synovial fluid is formed through a serum ultrafiltration process by cells that form the synovial membrane(synoviocytes). Synovial cells also manufacture hyaluronic acid (HA, also known as hyaluronate), aglycosaminoglycan that is the major noncellular component of synovial fluid. Synovial fluid supplies nutrients tothe avascular articular cartilage; it also provides the viscosity needed to absorb shock from slow movements, aswell as the elasticity required to absorb shock from rapid movements.

PathophysiologyPrimary and secondary osteoarthritis are not separable on a pathologic basis, though bilateral symmetry is oftenseen in cases of primary osteoarthritis, particularly when the hands are affected.[2, 21] Traditionally, osteoarthritiswas thought to affect primarily the articular cartilage of synovial joints; however, pathophysiologic changes arealso known to occur in the synovial fluid, as well as in the underlying (subchondral) bone, the overlying jointcapsule, and other joint tissues (see Workup).[22, 23, 24, 25]

Although osteoarthritis has been classified as a noninflammatory arthritis, increasing evidence has shown thatinflammation occurs as cytokines and metalloproteinases are released into the joint. These agents are involved inthe excessive matrix degradation that characterizes cartilage degeneration in osteoarthritis.[26] Therefore, it is nolonger appropriate to use the term degenerative joint disease when referring to osteoarthritis.

In early osteoarthritis, swelling of the cartilage usually occurs, because of the increased synthesis ofproteoglycans; this reflects an effort by the chondrocytes to repair cartilage damage. This stage may last for



years or decades and is characterized by hypertrophic repair of the articular cartilage.

As osteoarthritis progresses, however, the level of proteoglycans eventually drops very low, causing the cartilageto soften and lose elasticity and thereby further compromising joint surface integrity. Microscopically, flaking andfibrillations (vertical clefts) develop along the normally smooth articular cartilage on the surface of an osteoarthriticjoint. Over time, the loss of cartilage results in loss of joint space.

In major weightbearing joints of persons with osteoarthritis, a greater loss of joint space occurs at those areasexperiencing the highest loads. This effect contrasts with that of inflammatory arthritides, in which uniform jointspace narrowing is the rule.

In the osteoarthritic knee, for example, the greatest loss of joint space is commonly seen in the medialfemorotibial compartment, though the lateral femorotibial compartment and patellofemoral compartment may alsobe affected. Collapse of the medial or lateral compartments may result in varus or valgus deformities,respectively.

Erosion of the damaged cartilage in an osteoarthritic joint progresses until the underlying bone is exposed. Bonedenuded of its protective cartilage continues to articulate with the opposing surface. Eventually, the increasingstresses exceed the biomechanical yield strength of the bone. The subchondral bone responds with vascularinvasion and increased cellularity, becoming thickened and dense (a process known as eburnation) at areas ofpressure.[27]

The traumatized subchondral bone may also undergo cystic degeneration, which is attributable either to osseousnecrosis secondary to chronic impaction or to the intrusion of synovial fluid. Osteoarthritic cysts are also referredto as subchondral cysts, pseudocysts, or geodes (the preferred European term) and may range from 2 to 20 mmin diameter. Osteoarthritic cysts in the acetabulum (see the image below) are termed Egger cysts.

This radiograph demonstrates osteoarthritis of the right hip, including the finding of sclerosis at the superior aspect of the acetabulum.Frequently, osteoarthritis at the hip is a bilateral finding, but it may occur unilaterally in an individual who has a previous history of hiptrauma that was confined to that one side.

At areas along the articular margin, vascularization of subchondral marrow, osseous metaplasia of synovialconnective tissue, and ossifying cartilaginous protrusions lead to irregular outgrowth of new bone (osteophytes).Fragmentation of these osteophytes or of the articular cartilage itself results in the presence of intraarticularloose bodies (joint mice).

Along with joint damage, osteoarthritis may also lead to pathophysiologic changes in associated ligaments andthe neuromuscular apparatus. For example, lateral collateral ligament complex abnormalities are common in kneeosteoarthritis.

Pain mechanisms in osteoarthritis

Pain, the main presenting symptom of osteoarthritis, is presumed to arise from a combination of mechanisms,including the following:

Osteophytic periosteal elevationVascular congestion of subchondral bone, leading to increased intraosseous pressureSynovitis with activation of synovial membrane nociceptorsFatigue in muscles that cross the jointOverall joint contractureJoint effusion and stretching of the joint capsuleTorn menisciInflammation of periarticular bursaePeriarticular muscle spasmPsychological factorsCrepitus (a rough or crunchy sensation)Central pain sensitization



When the spine is involved in osteoarthritis, especially the lumbar spine, the associated changes are verycommonly seen from L3 through L5. Symptoms include pain, stiffness, and occasional radicular pain from spinalstenosis. Foraminal narrowing is caused by facet arthritic changes that result in compression of the nerve roots.Acquired spondylolisthesis is a common complication of arthritis of the lumbar spine.

EtiologyThe daily stresses applied to the joints, especially the weightbearing joints (eg, ankle, knee, and hip), play animportant role in the development of osteoarthritis. Most investigators believe that degenerative alterations inosteoarthritis primarily begin in the articular cartilage, as a result of either excessive loading of a healthy joint orrelatively normal loading of a previously disturbed joint. External forces accelerate the catabolic effects of thechondrocytes and further disrupt the cartilaginous matrix.[28, 29, 30, 31]

Risk factors for osteoarthritis include the following[32, 33, 34, 35] :

AgeObesity[36, 37, 38]TraumaGenetics (significant family history)Reduced levels of sex hormonesMuscle weakness[39]

Repetitive use (ie, jobs requiring heavy labor and bending)[40]InfectionCrystal depositionAcromegalyPrevious inflammatory arthritis (eg, burntout rheumatoid arthritis)Heritable metabolic causes (eg, alkaptonuria, hemochromatosis, and Wilson disease)Hemoglobinopathies (eg, sickle cell disease and thalassemia)Neuropathic disorders leading to a Charcot joint (eg, syringomyelia, tabes dorsalis, and diabetes)Underlying morphologic risk factors (eg, congenital hip dislocation and slipped femoral capital epiphysis)Disorders of bone (eg, Paget disease and avascular necrosis)Previous surgical procedures (eg, meniscectomy)

Advancing age

With advancing age come reductions in cartilage volume, proteoglycan content, cartilage vascularization, andcartilage perfusion. These changes may result in certain characteristic radiologic features, including a narrowedjoint space and marginal osteophytes. However, biochemical and pathophysiologic findings support the notion thatage alone is an insufficient cause of osteoarthritis.

Obesity

Obesity increases the mechanical stress in a weightbearing joint. It has been strongly linked to osteoarthritis ofthe knees and, to a lesser extent, of the hips. A study that evaluated the associations between body mass index(BMI) over 14 years and knee pain at year 15 in 594 women found that a higher BMI at year 1 and a significantincrease in BMI over 15 years were predictors of bilateral knee pain at year 15.[38] The association between BMIincrease and knee pain was independent of radiographic changes.

In addition to its mechanical effects, obesity may be an inflammatory risk factor for osteoarthritis. Obesity isassociated with increased levels (both systemic and intraarticular) of adipokines (cytokines derived from adiposetissue), which may promote chronic, lowgrade inflammation in joints.[41]

Other causes

Trauma or surgery (including surgical repair of traumatic injury) involving the articular cartilage, ligaments, ormenisci can lead to abnormal biomechanics in the joints and accelerate osteoarthritis. Although repairs ofligament and meniscal injuries usually restore joint function, osteoarthritis has been observed 515 yearsafterward in 5060% of patients.[42]

Insults to the joints may occur even in the absence of obvious trauma. Microtrauma may also cause damage,especially in individuals whose occupation or lifestyle involves frequent squatting, stairclimbing, or kneeling.

Muscle dysfunction compromises the body’s neuromuscular protective mechanisms, leading to increased jointmotion and ultimately resulting in osteoarthritis. This effect underscores the need for continued muscle toning



exercises as a means of preventing muscle dysfunction.

Valgus malalignment at the knee has been shown to increase the incidence and risk of radiographic progressionof knee osteoarthritis involving the lateral compartment.[43]

Genetics

A hereditary component, particularly in osteoarthritis presentations involving multiple joints, has long beenrecognized.[44, 45, 46] Several genes have been directly associated with osteoarthritis,[47] and many more havebeen determined to be associated with contributing factors, such as excessive inflammation and obesity.

Genes in the BMP (bone morphogenetic protein) and WNT (winglesstype) signaling cascades have beenimplicated in osteoarthritis. Two genes in particular, GDF5 (growth and differentiation factor 5) and FRZB (frizzledrelated protein) have been identified in the articular cartilage in animal studies and share a strong correlation withosteoarthritis.[48, 49, 50, 51]

Genomewide association studies (GWAS) have identified an association between osteoarthritis of large jointsand the MCF2L gene. This gene is key in neurotrophinmediated regulation of peripheral nervous system cellmotility.[52]

Genetic factors are also important in certain heritable developmental defects and skeletal anomalies that cancause congenital misalignment of joints. These may result in damage to cartilage and the structure of the joint.

Currently, clinical genetic testing is not offered to patients who have osteoarthritis unless they also have otheranomalies that could be associated with a genetic condition. In the future, testing may allow individualization oftherapeutics.

Epidemiology

United States and international statistics

Osteoarthritis affects more than 20 million individuals in the United States, though statistical figures areinfluenced by how the condition is defined—that is, by selfreport, by radiographic or symptomatic criteria, or by acombination of these.[53] On the basis of the radiographic criteria for osteoarthritis, more 50% of adults older than65 years are affected by the disease.

Internationally, osteoarthritis is the most common articular disease. Estimates of its frequency vary acrossdifferent populations.

Agerelated demographics

Primary osteoarthritis is a common disorder of the elderly, and patients are often asymptomatic. Approximately8090% of individuals older than 65 years have evidence of radiographic primary osteoarthritis.[54]

Symptoms typically do not become noticeable until after the age of 50 years. The prevalence of the diseaseincreases dramatically among persons older than 50 years, likely because of agerelated alterations in collagenand proteoglycans that decrease the tensile strength of the joint cartilage and because of a diminished nutrientsupply to the cartilage.[54]

Sexrelated demographics

In individuals older than 55 years, the prevalence of osteoarthritis is higher among women than among men.[54]Women are especially susceptible to osteoarthritis in the DIP joints of the fingers. Women also have osteoarthritisof the knee joints more frequently than men do, with a femaletomale incidence ratio of 1.7:1. Women are alsomore prone to erosive osteoarthritis, with a femaletomale ratio of about 12:1.

Racerelated demographics

Interethnic differences in the prevalence of osteoarthritis have been noted.[55] The disorder is more prevalent inNative Americans than in the general population. Disease of the hip is seen less frequently in Chinese patientsfrom Hong Kong than in agematched white populations. Symptomatic knee osteoarthritis is extremely common inChina.[56]

In persons older than 65 years, osteoarthritis is more common in whites than in blacks. Knee osteoarthritis



appears to be more common in black women than in other groups. Jordan et al found that in comparison withwhites, African American men and women had a slightly higher prevalence of radiographic and symptomatic kneeosteoarthritis but a significantly higher prevalence of severe radiographic knee osteoarthritis.[57]

PrognosisThe prognosis in patients with osteoarthritis depends on the joints involved and on the severity of the condition.No proven disease or structuremodifying drugs for osteoarthritis are currently known; consequently,pharmacologic treatment is directed at symptom relief.

A systematic review found the following clinical features to be associated with more rapid progression of kneeosteoarthritis[58] :

Older ageHigher BMIVarus deformityMultiple involved joints

Patients with osteoarthritis who have undergone joint replacement have a good prognosis, with success rates forhip and knee arthroplasty generally exceeding 90%. However, a joint prosthesis may have to be revised 1015years after its placement, depending on the patient’s activity level. Younger and more active patients are morelikely to require revisions, whereas the majority of older patients will not. (See Treatment.)

Patient EducationEducate patients on the natural history of and management options for osteoarthritis, emphasizing the benefits ofexercise and weight loss. Explain the differences between osteoarthritis and more rapidly progressive arthritides,such as rheumatoid arthritis.

Several Arthritis Foundation studies have demonstrated that education in osteoarthritis benefits the patient.Through education, patients can learn and implement strategies for reducing pain and improving joint function.Emphasize the need for physician followup visits.

For patient education information, see the Arthritis Center, as well as Osteoarthritis.

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Contributor Information and DisclosuresAuthorCarlos J Lozada, MD Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine,Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M MillerSchool of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians andAmerican College of Rheumatology

Disclosure: Pfizer Honoraria Consulting; AbbVie Grant/research funds Other; Heel Honoraria Consulting

Chief EditorHerbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of NewYork Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western PennsylvaniaHospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American Collegeof Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional ContributorsSamuel Agnew, MD, FACS Associate Professor, Departments of Orthopedic Surgery and Surgery, Chief of

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Orthopedic Trauma, University of Florida at Jacksonville College of Medicine; Consulting Surgeon, Departmentof Orthopedic Surgery, McLeod Regional Medical Center

Samuel Agnew, MD, FACS is a member of the following medical societies: American Association for theSurgery of Trauma, American College of Surgeons, Orthopaedic Trauma Association, and SouthernOrthopaedic Association


Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine,Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College ofPhysicians, and American College of Rheumatology


Siriporn Janchai, MD Fellow, Department of Medicine, Section of Physical Medicine and Rehabilitation,Louisiana State University Health Science Center


James Monroe Laborde, MD, MS Clinical Assistant Professor, Department of Orthopedics, Louisiana StateUniversity Health Sciences Center and Tulane Medical School; Adjunct Assistant Professor, Department ofBiomedical Engineering, Tulane University; Adjunct Assistant Professor, Department of Physical Medicine andRehabilitation, Louisiana State University Medical School

James Monroe Laborde, MD, MS is a member of the following medical societies: American Academy ofOrthopaedic Surgeons


Phillip J Marone, MD, MSPH Clinical Professor, Department of Orthopedic Surgery, Jefferson MedicalCollege

Phillip J Marone, MD, MSPH is a member of the following medical societies: American Academy ofOrthopaedic Surgeons, American College of Surgeons, American Medical Association, American OrthopaedicSociety for Sports Medicine, and Philadelphia County Medical Society


Furqan H Siddiqui, MD Assistant Professor of Medicine (Research), Louisiana State University MedicalCenter in New Orleans


Eli Steigelfest, MD Consulting Staff, Department of Rheumatology, The Consultant Group, PC


Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical CenterCollege of Pharmacy; EditorinChief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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