Approach to the adult with unspecified knee pain

INTRODUCTION — The knee has the largest articulating surface of any joint. Depending on the activity, this weight-bearing joint can support two to five times a person's body weight. Chronic knee pain affects 25 percent of adults and has a deleterious effect on daily function and quality of life [1,2].

The general evaluation of the adult presenting with undifferentiated knee pain is discussed here, including details about differentiating among the causes of knee pain based upon the history and examination findings. For cases where knee pain develops following acute, low-energy trauma or chronic overuse, often in athletes or active adults, and is most likely musculoskeletal in origin, a separate in-depth discussion of how to approach such patients is provided. (See "Approach to the adult with knee pain likely of musculoskeletal origin".)

BASIC KNEE ANATOMY AND BIOMECHANICS — The anatomy and basic biomechanics of the knee are reviewed separately. (See "Physical examination of the knee", section on 'Anatomy'.)

HISTORY OVERVIEW AND DIAGNOSTIC CATEGORIES — History-taking for the active adult presenting with knee pain is discussed in detail separately, but several aspects of the history warrant emphasis. (See "Approach to the adult with knee pain likely of musculoskeletal origin", section on 'History'.)

First, the differential diagnosis for knee pain is complex and obtaining a clear history remains essential for diagnosis. The following flow chart provides an overview of how to approach the diagnosis of knee pain in the adult (algorithm 1). Information from the history helps the clinician to distinguish among five diagnostic categories:

●Acute knee pain following recent trauma or overuse

●Atraumatic knee pain associated with joint effusion

●Atraumatic knee pain NOT associated with joint effusion

●Referred knee pain

●Uncommon causes of knee pain

Several questions in particular are important for narrowing the differential diagnosis and should be asked of every adult patient presenting with knee pain:

●Did pain begin following an acute traumatic event? Pain immediately following an injury is concerning for possible structural damage to the knee. Delayed pain suggests tendon strains, cartilage contusions, or minor soft tissue tears. The closer the pain onset is to the specific event, the higher the likelihood of significant structural damage.

●Is the pain associated with activity (eg, new exercise regimen, change in previous training habits, day-to-day activity over the preceding few months)? Pain associated with activity should lead to further inquiry about training equipment (eg, shoes, braces), training volume (eg, training days per week, duration of training sessions), intensity, and any recent changes in such parameters. Information about specific activities that trigger pain can be helpful. As an example, anterior knee pain associated with sprinting or jumping is a classic part of the history of patellar tendinopathy.

●In which anatomic quadrant is the pain located (anterior, posterior, lateral, or medial), or is the pain diffuse or vague? Localizing knee pain to an anatomic quadrant or more specific location helps circumscribe the differential diagnosis. Pinpoint localization is generally possible following trauma to a specific ligament, tendon, or other palpable anatomic structure. Pain described as diffuse or vague may be secondary to injury of an intra-articular structure, a rheumatologic or infectious process, or from referred pain.

●Has the painful knee been swollen (ie, joint effusion) or erythematous? Rapid swelling after trauma occurs with bleeding into the knee joint and suggests a significant injury (eg, anterior cruciate ligament tear). Swelling or erythema occurring without trauma may indicate an infectious, rheumatologic, or crystal-induced condition and diagnostic arthrocentesis is often indicated.

●Are constitutional symptoms, such as fevers, chills, night sweats, fatigue, or rash, present? The presence of such symptoms and signs suggests a systemic illness and further investigation of infectious, autoimmune, or neoplastic causes is necessary.

●Is there a history of prior knee injury or surgery? A past history of knee injury is the most accurate predictive risk factor for future knee injury. The clinician should inquire about the type of injury, duration of disability, and the rehabilitation program. Often, a new knee injury is a complication of an old or concurrent injury. As an example, patellofemoral pain can develop in patients who alter their running gait due to discomfort from chronic Achilles tendinopathy. Likewise, prior surgical repairs can "wear out" or fail, leading to recurrence of the initial condition. All patients with prior injury or surgery experience some degree of deconditioning while injured and recovering. This deconditioning, combined with poor or incomplete rehabilitation, predisposes to new injuries.

●Are there symptoms affecting any other joints? Subjective symptoms and/or examination findings that reveal multiple affected joints raise suspicion for a systemic or rheumatologic process.

●Is there a history of systemic or rheumatologic disease? A known history of a systemic or rheumatologic disease can help to guide clinical inquiry, physical examination, and possible laboratory testing.

PHYSICAL EXAMINATION OF THE KNEE — An in-depth discussion of the physical examination of the knee is provided separately (see "Physical examination of the knee"). A few points about the knee examination are worth highlighting:

●When examining the knee, look closely for discrepancies in strength and range of motion between the painful and asymptomatic joints.

●Try to reproduce the patient's presenting pain complaint. Many examination maneuvers cause some discomfort, even when performed on asymptomatic limbs. Therefore, it is important to use only the most appropriate maneuvers (based on the most likely potential diagnoses as determined by the history) to reproduce the patient’s symptoms as precisely as possible. This approach is most likely to pinpoint the cause of the discomfort. Pain elicited by the examination that is different than the presenting complaint may be worth noting, but it is often unrelated to the diagnosis.

●Perform the knee examination systematically. By performing the examination in the same manner every time, the risk of overlooking an important finding is reduced. Traditionally the musculoskeletal examination is performed in the following order: inspection, palpation, range of motion, strength, neurovascular, and "special tests" (maneuvers to assess a specific diagnosis).

INITIAL STEPS TO CATEGORIZING KNEE PAIN

Step one: Distinguish acute versus chronic pain — For most musculoskeletal conditions, pain of less than six weeks duration is classified as acute or subacute, while pain lasting longer than six weeks is classified as chronic. This is by convention, as there is no high-quality evidence supporting this threshold. However, most minor musculoskeletal ailments resolve within six weeks of onset with appropriate activity modification. The following flow chart provides an overview of how to approach the diagnosis of knee pain in the adult (algorithm 1).

Acute knee pain may stem directly from trauma (easily identified by the history in most cases) or from regular activity (eg, overuse injury), or it may be unrelated to trauma or activity. It is important to determine whether the onset of pain was abrupt or insidious. As an example, it is helpful to know that a patient's pain started abruptly eight weeks ago while running and has not fully abated. While technically a chronic pain presentation (greater than six weeks duration), this presentation is consistent with a specific event that caused the acute onset of pain. In cases involving an abrupt onset or sudden change in knee pain, the clinician should focus on clarifying the events leading up to the onset.

Some patients complain of a sudden worsening or change in a long-standing pain (ie, acute on chronic pain pattern). This suggests an overuse injury that has been exacerbated by activity.

Step two: Distinguish traumatic versus nontraumatic pain — The next step is to determine whether an acute injury has occurred. Generally, this is obvious from the history. Common examples include a fall, a direct blow to the knee, or a motor vehicle crash. However, direct contact is not necessary for a person to sustain an acute traumatic knee injury. Adults may experience acute pain after non-contact trauma, such as running, jumping, squatting, slipping on ice without falling, or abruptly twisting their knee. Thus, clinicians should inquire about both contact and non-contact trauma.

Step three: Determine whether an effusion is present — Determining the presence or absence of a joint effusion is an important part of assessing the patient with knee pain. The method for detecting an effusion is described separately. (See "Physical examination of the knee", section on 'Detection of an effusion'.)

An important adjunct to the physical examination for detecting an effusion is the use of musculoskeletal ultrasound (MSK US). Moderate to large volume effusions (20 mL or more) are readily detected by manual examination; however, small effusions can be missed. MSK US is nearly 100 percent sensitive and specific for detecting knee effusions. This becomes important with small effusions (5 to 10 mL), which are clinically significant but can be difficult to detect by physical examination alone (especially in obese or muscular patients) [3]. (See "Musculoskeletal ultrasound of the knee".)

The presence of a knee joint effusion following acute trauma suggests the presence of structural damage to bone, cartilage, or a ligament. Nontraumatic knee effusions unrelated to activity, warrant a more thorough workup, as the differential diagnosis includes an infected (ie, septic) joint. (See 'Conditions NOT related to activity' below.)

Step four: Determine pain location — Determining the primary location of knee pain is useful in all cases, but it is particularly important when evaluating patients with nontraumatic knee pain and no joint effusion. The location of the knee pain (anterior, medial, lateral, or posterior) helps to inform the differential diagnosis. Ask the patient to point with one finger to the precise location of the pain.

ACUTE KNEE PAIN ASSOCIATED WITH TRAUMA — The diagnostic approach to the patient with knee pain following acute trauma is reviewed in detail separately. Clinicians evaluating patients with such a presentation, regardless of the patient’s baseline activities or whether the trauma involved physical exertion, are referred to that discussion. (See "Approach to the adult with knee pain likely of musculoskeletal origin", section on 'Acute knee pain associated with trauma'.)

The differential diagnosis for acute knee pain following trauma associated with an effusion includes the injuries listed below (table 1). Note that trauma for the purposes of this discussion refers primarily to low-energy trauma (as opposed to high-energy trauma, such as a motor vehicle crash). Patients with knee pain following high-energy trauma may have significant internal injuries and should be evaluated in the emergency department. (See "Initial management of trauma in adults".)

Common causes of knee pain following acute, low-energy trauma:

●Medial or lateral collateral ligament tear

●Anterior cruciate ligament tear

●Meniscus tear

●Patella dislocation or significant subluxation

●Patella tendon tear

●Intra-articular fracture

●Osteochondral defect

Less common causes of knee pain following acute, low-energy trauma:

●Bone contusion

●Posterolateral corner injury

●Posterior cruciate ligament tear

●Quadriceps tendon tear

●Fibular head or neck fracture

●Patella fracture

●Knee (tibiofemoral) dislocation

CONDITIONS NOT INVOLVING ACUTE TRAUMA — Identifying the cause of nontraumatic knee pain can be challenging. Determining whether the knee pain is associated with activity, and whether an effusion is present, are important early steps in narrowing the differential diagnosis. A table summarizing the major diagnoses to consider and their distinguishing features is provided (table 2). The following flow chart provides an overview of how to approach the diagnosis of knee pain in the adult (algorithm 1).

Nontraumatic conditions associated WITH a joint effusion

Conditions made worse by activity — The differential diagnosis of nontraumatic knee pain associated with an effusion can be narrowed based on the association with activity. Important, common causes of nontraumatic knee pain that increase acutely with activity include osteochondral defects and osteoarthritis.

●Articular cartilage (osteochondral) injury or defect – Osteochondral defects are usually caused by significant knee trauma but may be secondary to milder trauma or chronic overuse (eg, osteochondritis dissecans). Patients with such defects often describe diffuse knee pain that is worse during and after activity. A knee effusion brought on by activity is an important historical clue, as spontaneous effusions unrelated to activity generally do not occur with osteochondral defects. Imaging studies (often magnetic resonance imaging [MRI]) or arthroscopy are required to diagnose osteochondritis dissecans and other osteochondral defects.

●Osteoarthritis – Osteoarthritis (OA) involves degradation and thinning of the articular cartilage, and OA of the knee is a leading cause of pain and disability worldwide [4]. OA can present as diffuse or localized knee pain, with or without an effusion. Intermittent effusions occur in persons with OA when they increase their activity. Patients with an OA flare often describe a delayed onset to their effusion, which develops 12 to 24 hours following the acute event. Vague or diffuse joint line tenderness, intact ligaments, and non-focal meniscus tests comprise the typical constellation of examination findings associated with OA flares. In addition, many patients are unable to fully flex or extend the affected knee (picture 1).

Strongly associated risk factors can help to identify patients in whom knee OA is the most likely diagnosis, these include: age over 50 years, female gender, higher body mass index, previous knee injury or knee surgery, malalignment, joint laxity, occupational or recreational activities that place stress on the knee, family history, and the presence of Heberden's nodes (picture 2) [5]. (See "Clinical manifestations and diagnosis of osteoarthritis".)

There is often poor correlation between radiographic changes (image 1 and image 2 and image 3) and a person's symptoms [4]. Therefore, the diagnosis of knee OA remains a clinical one and radiographs should not be used as the sole basis for diagnosing OA. The diagnosis of knee OA can be made without the use of radiographs or in patients with normal radiographic findings, if each the following are present [5]:

•Age at least 40 years old

•Activity-related joint pain

•Minimal or no morning stiffness

•Functional limitations, such a declining ability to walk distances or to climb stairs

•One or more typical examination findings (eg, crepitus, restricted joint movement, bony enlargement)

If a palpable effusion is present, joint aspiration and synovial fluid testing may be needed to exclude inflammatory disease. The indications for synovial fluid testing are discussed in greater detail separately. (See "Synovial fluid analysis".)

Conditions NOT related to activity — Knee pain associated with a joint effusion, despite the absence of any trauma or activity that exacerbates symptoms, is a concerning finding, and indicates the need for a more extensive workup. In addition to a careful history and examination, plain radiographs and knee joint aspiration are often necessary. Important causes of nontraumatic knee pain that is not associated with activity include:

●Crystal arthropathy

●Infectious (septic) arthritis (medical emergency)

●Disseminated gonococcal infection

●Systemic rheumatic disease

●Crystal arthropathy – Crystal arthropathy can present as unilateral arthritis, which may include acute knee pain and effusion not related to trauma or activity. Local erythema, warmth, joint pain, and an effusion are common examination findings. Calcium pyrophosphate crystal deposition (CPPD) disease (ie, pseudogout) most often affects the knee, while gouty arthritis most often involves in the first metatarsophalangeal joint or midfoot, although knee involvement is common. A serum uric acid level should not be used to diagnose an acute gouty flare, as up to a third of such patients have a normal serum uric acid concentration. While a serum white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein may be useful for the management of these patients, they should never substitute for joint aspiration and synovial fluid analysis. Increasingly, imaging techniques including ultrasound and dual-energy CT scanning are proving useful in the diagnosis of crystal arthropathy. (See "Clinical manifestations and diagnosis of gout" and "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease".)

●Infectious (septic) arthritis – Similar to crystal arthropathy, infectious arthritis of the knee typically presents with local erythema, warmth, joint pain, and an effusion. However, distinguishing between the two is crucial. Even among patients with risk factors and clinical findings consistent with crystal arthropathy or other non-infectious causes of knee pain, infectious arthritis must be ruled out if it is among the diagnoses entertained. Bacterial joint infection (ie, septic arthritis) is a medical emergency, as extensive cartilage damage can occur within hours of infection onset.

Definitive diagnosis is made by joint aspiration and fluid analysis. Joint fluid is evaluated for color and consistency, and sent to the lab for cell counts with differential, gram stain, culture, and crystal analysis. Synovial fluid analysis for glucose, protein, and lactate dehydrogenase (LDH) has limited utility. However, in patients being treated with antibiotics, such analysis may be useful. In these patients, the resultant Gram stain and culture may be negative, but a markedly reduced synovial fluid glucose increases the suspicion for infectious arthritis.

Elevations of synovial WBC counts above 100,000 per high-powered field (HPF), with polymorphonuclear cells (neutrophils) comprising more than 90 percent (ie, left shift), is most predictive of bacterial joint infection, though infection may be present with lower WBC counts. Additional testing may be warranted based on clinical suspicion and patient risk factors. Synovial fluid analysis and the septic joint are discussed in greater detail separately. (See "Septic arthritis in adults" and "Synovial fluid analysis".)

●Disseminated gonococcal infection (DGI) – DGI can develop in up to 3 percent of patients infected with Neisseria gonorrhoeae. Most such patients are younger than 40 years, but the condition occurs in both men and women. Presenting features of DGI include either a triad of abrupt onset of polyarthralgia (non-symmetric), tenosynovitis (particularly the wrist, fingers, ankles and toes), and painless dermatitis, or an asymmetric polyarticular or monoarticular purulent arthritis without skin manifestations, in which case the knee is the most common site. Neisseria gonorrhoeae is one of many organisms that can cause knee pain due to infection and inflammation. (See "Disseminated gonococcal infection".)

●Systemic rheumatic disease – Systemic rheumatic disease is a group of systemic autoimmune diseases that include: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s disease (SjD), systemic sclerosis, polymyositis, and dermatomyositis. RA is the most prevalent disease in this group. The presence of systemic symptoms, such as fevers, chills, night sweats, fatigue, or unintentional weight loss suggests infection, systemic disease, or cancer. Therefore, in these patients a more general history and a thorough physical examination should be performed looking for causes other than primarily musculoskeletal ones. Additional lab testing and diagnostic imaging may be necessary. (See 'Bone tumors' below and "Clinical manifestations of rheumatoid arthritis" and "Clinical manifestations of Sjögren’s disease: Extraglandular disease" and "Clinical manifestations of Sjögren's disease: Exocrine gland disease" and "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults" and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)

RA and SLE typically cause symmetric polyarthralgia or polyarthritis that may include bilateral knee pain and swelling. Over 65 to 90 percent of patients with SLE have arthritis, arthralgias or both. Any patient presenting with polyarticular, symmetric, or migrating pain, joint swelling, systemic symptoms (fever), or a positive family history may need a workup for a systemic rheumatic disease.

Nontraumatic conditions NOT associated with joint effusion — For many patients with knee pain there is no association with acute trauma and no history or clinical findings of a knee effusion. In these patients, the first step is to determine if the pain is exacerbated by activity. Some of the conditions listed below may cause some localized swelling, or an intermittent effusion, but nearly always this occurs with activity. It is important to ask patients that do not participate in regular physical exercise or labor if something in their day-to-day activity has changed (new job, recent vacation, recent work around the house, etc). The second and more important step is to pinpoint the location of the pain, if possible.

The differential diagnosis for knee pain unrelated to acute trauma or joint effusion is extensive, and therefore, the history and physical examination should be used to categorize the pain anatomically and narrow the list of potential diagnoses. A table summarizing the major diagnoses and their distinguishing features, and organized by pain location, is provided (table 3).

In summary, the key questions when evaluating these patients include:

●Is this an acute or chronic problem (six weeks is the standard threshold for chronic knee pain)?

●Has your activity level changed significantly in the three months leading up to the onset of pain?

●Using a single finger, can you point to the area where the pain is focused?

For the conditions listed below, joint aspiration and serum laboratory studies are rarely indicated, and radiographs are often unnecessary for making the diagnosis.

Anterior knee pain — Pain at the anterior knee is the most common complaint among patients presenting with atraumatic knee pain without an effusion. Such pain often stems from a specific structure and therefore the patient can either "point with one finger" to the painful site, or the clinician can recreate the pain with focused palpation. The conditions causing such pain include Osgood-Schlatter disease, Hoffa's fat pad syndrome, patellar and quadriceps tendinopathy (tendinosis), bursitis, and plica syndrome. Important structures to palpate in patients with anterior pain include the patella, patellofemoral joint, patellar tendon, tibial tubercle, and quadriceps tendon (picture 3).

●Osgood-Schlatter disease – Pain from Osgood-Schlatter disease is caused by tibial tubercle apophysitis at the insertion of the patellar tendon. The condition is most common in active older children and adolescents, but some adults may experience ongoing pain after the apophysis has fused. Pain and tenderness are localized to the tibial tubercle (figure 1 and figure 2 and picture 4). Pain increases with activity, particularly jumping and running. Poor flexibility of the quadriceps, and possibly the hip flexors, may be noted. (See "Osgood-Schlatter disease (tibial tuberosity avulsion)".)

●Hoffa's fat pad syndrome – The infrapatellar (ie, Hoffa's) fat pad (IFP) is a highly innervated and vascularized extra-articular structure located distal to the patella and directly beneath the patellar tendon. Edema within the fat pad can be painful and has been implicated in patellofemoral maltracking; patients with a diagnosis of patellofemoral pain (PFP) should be evaluated for possible IFP involvement [6]. IFP-related pain generally presents as anterior knee pain distal to the patella. It is often made worse by sprinting activities or squatting, and shares historical characteristics with patellar tendinopathy and PFP.

While no special tests are available to diagnose IFP, the physical examination may help to distinguish it from alternative diagnoses. Knee inspection is usually unremarkable, but inflammation of the IFP may be noted as asymmetric swelling of the patellar tendon. IFP syndrome should not cause visible maltracking of the patella during knee flexion or extension. Maneuvers that impinge the IFP, such as squatting or direct downward pressure on the patellar tendon, reproduce the patient’s anterior knee pain. Tenderness with palpation deep to the patellar tendon on either side, but not at its insertion, suggests inflammation and edema of the IFP [7]. Musculoskeletal ultrasound can be used to demonstrate that the patellar tendon, bursa, and other adjacent structures appear normal, and may reveal signs suggestive of IFP pathology. (See "Musculoskeletal ultrasound of the knee".)

●Quadriceps and patellar tendinopathy – The distal quadriceps tendon is a conjoined tendon of the vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris muscles. As it proceeds distally, the quadriceps tendon envelops the patella and becomes the patellar tendon distally, inserting on the anterior tibial tubercle. Both the quadriceps and patellar tendon are susceptible to many of the same conditions and injuries. Explosive movements involving knee extension, such as jumping, running, or squatting (eccentric stress) reproduce the pain associated with both quadriceps and patellar tendinopathy. Quadriceps tendinopathy, the more common condition, characteristically causes pain proximal to the superior patellar pole. Physical examination findings include focal pain with resisted knee extension and often some atrophy of the quadriceps muscle (typically the vastus medialis) on the involved side in comparison with the unaffected leg. Focal tenderness with direct palpation at, or just proximal to, the superior patellar pole is characteristic. In contrast, patellar tendinopathy causes pain distal to the patella. Focal tenderness at or just distal to the inferior patellar pole is common. (See "Quadriceps muscle and tendon injuries", section on 'Quadriceps tendinopathy'.)

The quadriceps and patellar tendons are visualized readily with ultrasound, which can be used as an adjunct to the physical examination for diagnosing tendinopathy. Tendinopathic changes visualized on ultrasound may include loss of the normal fibrillar structure of the tendon with reduced echogenicity, tendon thickening, and possibly calcific tendinopathy. (See "Musculoskeletal ultrasound of the knee".)

●Bursitis – Acute prepatellar or superficial infrapatellar bursitis presents with localized redness, swelling, and marked tenderness anterior to the patella or patellar tendon. The condition is usually associated with a history of direct trauma or repetitive pressure (prolonged kneeling) at the patellar region but may also be crystal-induced or due to a bacterial infection. Examination reveals pre-patellar swelling and edema between the skin and the patella. Ultrasound examination can be used to assess the anatomic relations of the above structures, and the exact location of bursitis. Care should be taken to not compress the superficial structures when performing the examination. The motion and stability of the knee joint itself remain unaffected by bursitis. (See "Knee bursitis" and "Musculoskeletal ultrasound of the knee".)

●Plica syndrome – Individuals who have sustained trauma to the medial peripatellar area or dislocations or subluxations of the patella may develop thickening of the medial patellar plica [8]. This condition can also develop chronically from overuse, particularly in runners with some degree of genu valgus ("knock knees"). A thickened medial plica may catch at the medial edge of the patella or the medial femoral condyle causing localized anteromedial knee pain that increases with movement, and possibly chondral injury. Examination reveals thickening of the plica (palpable in most patients) with focal tenderness at the medial underside of the patella. Ultrasound can be used to visualize thickened plica tissue. A useful examination maneuver is the medial patellar plica test (figure 3). (See "Plica syndrome of the knee".)

The causes of anterior knee pain listed above are often readily diagnosed by history and examination. The causes listed below—patella subluxation, PFP, chondromalacia patella, and patellar stress fracture—present without acute trauma or joint effusion, and do not lend themselves to pinpoint localization.

●Chronic patella dislocation or subluxation – Patients with a history of patellar dislocation have damaged the medial patellofemoral ligament and thus are at increased risk for recurrent or chronic subluxation and dislocation (figure 4). These patients typically describe anteromedial patellar discomfort and a sensation of the knee snapping or giving way during activity. Examination often reveals atrophy of the vastus medialis and a positive apprehension test (figure 5). Individuals with hypermobility disorders, such as Ehlers-Danlos Syndrome, are at risk for chronic patella subluxation. (See "Recognition and initial management of patellar dislocations".)

●Patellofemoral pain (PFP) – PFP is a frequently encountered overuse disorder that involves the patellofemoral region and often presents as anterior knee pain. PFP is diagnosed primarily from the history and is characterized by pain around or behind the patella that cannot be attributed to another discrete intra-articular (eg, meniscus tear) or peripatellar (eg, patellar tendinopathy) pathology. PFP is aggravated by one or more activities that involve loading the patellofemoral joint during weight bearing on a flexed knee. Common historical features include vague, poorly localized anterior knee pain (usually "under" or around the patella) that is made worse with squatting, running, prolonged sitting (theater sign), or going up or down stairs. Mechanical symptoms (eg, locking, catching) and the presence of an effusion are NOT associated with PFP. Many people with PFP report instability or their knee "giving out", which stems from pain causing reflex inhibition of the quadriceps. It bears emphasis that patellar instability and ligamentous injury of the knee should be ruled out by examination before ascribing the patients symptoms to PFP. Ultrasound can be used to assess peripatellar structures of the knee and to help rule out other diagnoses. However, there are no ultrasound-specific changes or criteria for diagnosing PFP. (See "Patellofemoral pain" and "Musculoskeletal ultrasound of the knee".)

●Chondromalacia patella – Chondromalacia patella is a cause of peripatellar pain and the term is commonly used interchangeably with PFP. However, chondromalacia patella is a distinct radiologic diagnosis defined by the presence of pathologic changes in the articular cartilage on the underside of the patella, such as softening, erosion, and fragmentation [9]. The clinical history and examination findings are similar to PFP, but an effusion may also be present if articular cartilage damage is sufficiently severe. The articular damage is usually secondary to a prior injury or chronic maltracking of the patella in the trochlear groove. MRI is needed to make the diagnosis but is usually unnecessary as treatment is similar to that for PFP.

●Patella stress fracture – Patella stress fractures develop after repeated application of submaximal stress leading to cortical disruption and pain. These fractures are seen in highly active individuals participating in explosive jumping or plyometric activities, and does not occur in sedentary individuals or "weekend warriors." Often, there is an abrupt increase in the volume or intensity of exercise or athletic training several weeks prior to the onset of pain. Although rare, patella stress fractures are considered to be at high risk for nonunion and should be referred to a provider with expertise in musculoskeletal medicine [10]. The history and examination findings are often nonspecific in the early stages, but pain becomes more localized to the patella as the injury progresses. Ultrasound can be used to evaluate for acute patellar fracture or bipartite patella; however, it is not sensitive or specific for stress fracture. MRI is typically needed to make a definitive diagnosis. (See "Overview of stress fractures" and "Approach to chronic knee pain or injury in children or skeletally immature adolescents", section on 'Patellar stress fracture'.)

Medial knee pain — Medial knee pain unrelated to trauma or a joint effusion may be due to a degenerative tear of the medial meniscus or to other conditions. Important structures to palpate include the medial joint line, medial (tibial) collateral ligament, and pes anserine bursa.

●Degenerative medial meniscal tear – Degenerative medial meniscal tears are common in older patients, as the medial compartment of the knee absorbs the most force during walking, running, and squatting (figure 6 and figure 7). Although a common finding on MRI, degenerative meniscal tears (both medial and lateral), are often asymptomatic. Findings that suggest a meniscal tear is the source of pain include medial or diffuse knee pain, mechanical symptoms (catching, locking, inability to extend the knee completely), swelling (especially after activity), and increased pain with squatting. Examination findings consistent with a meniscal tear include medial joint line tenderness (especially posterior to the medial collateral ligament), positive McMurray test, and a positive Thessaly test. It is important to ask whether the pain elicited during a provocative maneuver of the knee (eg, McMurray test) is the same as the pain that the patient has been experiencing and caused them to seek medical attention. A thorough history and examination are typically sufficient to make the diagnosis, and advanced imaging is generally unnecessary. (See "Meniscal injury of the knee".)

●Saphenous nerve entrapment – The saphenous nerve is the largest cutaneous branch of the femoral nerve (figure 8). It traverses the adductor canal and its infrapatellar branch innervates the skin over the medial and anterior portion of the knee. Entrapment at the adductor canal, or anywhere along the nerve’s path thereafter, can cause medial knee pain [11]. Such pain is characterized by allodynia (pain provoked by a typically benign stimulus) and radiation along the course of the saphenous nerve, and is worsened by palpation or tapping at the site of entrapment (Tinel's maneuver). Pain is generally NOT related to activity and the person may complain of positional pain. Consider this diagnosis in patients with chronic medial knee pain that is not consistently associated with activity, refractory to treatment, and associated with unremarkable imaging studies. A skilled sonographer can perform an ultrasound examination of the saphenous nerve. The pathologic nerve may be thickened and/or surrounded by fluid. A saphenous nerve block can relieve symptoms and confirm the diagnosis.

●Pes anserine bursitis – The pes anserine tendons and underlying bursa are readily identified, and should be palpated in patients presenting with anterior or medial knee pain. The pes anserine is located on the proximal anteromedial aspect of the tibia and is the common tendinous insertion of the sartorius, gracilis, and semi-tendinosis muscles (picture 5). Pain from pes anserine bursitis is usually of insidious onset and located on the medial side of the knee. It is worse with exercise (especially running) or ascending stairs. Pes anserine bursitis is common in older patients with osteoarthritis and less common among younger individuals. Examination may reveal tenderness over the medial joint line, similar to a medial meniscal injury, for which it is commonly mistaken. However, the point of maximum tenderness in patients with pes anserine bursitis is at or near the insertion of the pes anserine tendon on the tibia, which is anterior and distal to the medial joint line. While there may be focal swelling of the bursa at the tendon insertion point, knee swelling or effusion is NOT caused by pes anserine bursitis. Although the pes anserine bursa is readily seen on ultrasound, such evaluation is generally not needed for diagnosis or treatment. (See "Knee bursitis".)

Lateral knee pain — Lateral knee pain unrelated to trauma or a joint effusion may be due to iliotibial band syndrome, a degenerative tear of the lateral meniscus, or to other conditions. Important structures to palpate include the lateral joint line, lateral femoral condyle, and the lateral collateral ligament (LCL).

●Iliotibial band syndrome (ITBS) – Chronic atraumatic lateral knee pain is often caused by ITBS. The ITB is a fibrous band that runs longitudinally along the lateral aspect of the thigh from its origin at the iliac crest to its insertion on the proximal tibia (at Gerdy’s tubercle) (figure 9). An aching or burning pain and focal tenderness at the site where the band courses over the lateral femoral condyle (pain is not at the insertion on the tibia or at the lateral joint line) characterizes ITBS, which occurs predominately in runners, but may develop in cyclists due to overuse or improper seat height. The history may include downhill running or walking, or running the same direction on cambered roads (most roads have a slight slant to them eliciting a functional leg length discrepancy if one runs the same direction on the same road consistently), all of which aggravate the ITB. A suggestive history, focal tenderness at the lateral femoral condyle, and a positive Noble compression test suggest the diagnosis. (See "Iliotibial band syndrome".)

Ultrasound examination can be helpful for diagnosing ITBS. Tendinopathic changes, including loss of the normal fibrillar structure of the tendon, along with reduced echogenicity and tendon thickening, can be seen. Furthermore, dynamic assessment of the ITB during knee flexion and extension may reveal "snapping or friction" of the tendon over the lateral femoral condyle. (See "Musculoskeletal ultrasound of the knee".)

●Degenerative lateral meniscal tear – Degenerative lateral meniscal tears are less common than medial meniscal tears, but the clinical presentation and examination findings are similar. Examination should include palpation of the ITB over the lateral femoral condyle and Noble’s compression test to rule out ITBS. (See 'Medial knee pain' above and "Meniscal injury of the knee".)

Posterior knee pain — Posterior knee pain unrelated to trauma or a joint effusion may be due to popliteal artery aneurysm or entrapment, popliteal (Baker's) cyst, or tendinopathy (tendinosis). The important area to palpate is the popliteal fossa (both for a mass and a pulse).

●Popliteal artery aneurysm – Generally seen in older individuals with risk factors for cardiovascular disease (eg, hypertension, smoking), popliteal artery aneurysms may present with chronic or acute posterior knee pain (picture 6 and figure 10). Small aneurysms may be asymptomatic, but symptomatic aneurysms can present with signs of claudication or acute limb-threatening ischemia from arterial thrombosis. A large pulsatile mass noted in the popliteal fossa is consistent with this diagnosis. Ultrasound can be used to look for an aneurysm in the popliteal fossa. Comparison to the contralateral side is easily done. If this diagnosis is possible, patients should be referred for appropriate advanced diagnostic imaging. A substantial percentage of patients with a popliteal artery aneurysm have an abdominal aortic aneurysm and screening is warranted. (See "Popliteal artery aneurysm".)

●Popliteal artery entrapment – Unlike popliteal artery aneurysm, popliteal artery entrapment is a rare cause of posterior knee pain typically seen in athletic individuals (men more often than women) that is NOT suggestive of underlying cardiovascular disease (picture 6). Patients typically complain of a deep pain in the calf or popliteal fossa, and claudication type symptoms during vigorous activities involving repeated ankle dorsiflexion and plantarflexion [12]. Patients are typically asymptomatic at rest with a normal resting physical examination. Awareness of this entity and a high index of suspicion are important because tailored imaging studies are required to make the diagnosis. (See "Calf injuries not involving the Achilles tendon", section on 'Popliteal artery entrapment'.)

●Popliteal "Baker's" cyst – A popliteal (or Baker's) cyst often presents as posterior knee pain and swelling, which can be abrupt or insidious in onset (picture 7). The swelling is localized to the posterior capsule and is not a true joint effusion; however, it is typically joint fluid that is contained in the cyst. Swelling usually worsens after exercise, especially activities involving repetitive knee flexion or squatting. Some patients have cyst formation without knee pain. Examination commonly reveals a palpable, non-pulsatile cystic structure in the popliteal fossa during knee extension that disappears with knee flexion. Ultrasound examination reveals a fluid-filled mass at the intersection of the medial gastrocnemius and semimembranosus tendons. (See "Popliteal (Baker's) cyst".)

●Popliteus tendinopathy – The popliteal tendon can be injured, along with other structures in the posterolateral corner, during acute trauma. However, popliteal tendinopathy (or tendinosis) can develop chronically, most often in people who do a lot of downhill running or walking. Pain is described as a deep ache or sharp pain exacerbated by performing downhill activities. Typically, pain can be elicited by palpating the popliteal tendon origin just anterior to the lateral femoral condyle and LCL. This is done more easily if the patient crosses their legs in a "figure-of-four" position. The primary function of the popliteus is tibial internal rotation; therefore, symptomatic patients experience pain with resisted internal rotation (Garrick's test) or passive external rotation of the tibia. (See "Calf injuries not involving the Achilles tendon", section on 'Popliteus tendinopathy'.)

BONE TUMORS — Primary bone tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma, as well as metastatic tumors to bone, are rare, but important causes of knee pain. Patients complain of localized low-level pain, with possible swelling, in the area of the tumor. A joint effusion may be present if the tumor is intra-articular. Systemic symptoms, such as fevers, chills, night sweats, and unintentional weight loss, may be present but are not universal findings. Pain that is worse at night is a concerning finding that should prompt an in-depth workup. Plain radiographs are helpful to look for bony tumors. (See "Bone tumors: Diagnosis and biopsy techniques", section on 'Clinical presentation'.)

REFERRED PAIN — Patients with pain that originates from disorders of the back, sacroiliac joint, or hip may present with knee pain referred from the actual source. The fifth lumbar (L5) nerve root and sacroiliac joint can refer pain to the popliteal space. The first sacral (S1) nerve root, hip joint, trochanteric bursa, and femur can refer pain along the lateral thigh to the lateral aspect of the knee [13]. Patients with referred pain typically struggle to localize or describe their symptoms. The knee examination lacks focal tenderness or inflammatory changes, and flexion and extension of the knee are normal, or symmetric with the asymptomatic joint.

OTHER INFREQUENT CAUSES OF KNEE PAIN — These rare causes of knee pain should be considered on the differential of persistent unexplained knee pain, especially when objective findings of the knee are vague.

Systemic conditions — A number of systemic conditions may present with musculoskeletal manifestations, including arthralgias and knee pain, early in the disease course. These include thyroid disease, primary hyperparathyroidism, hemochromatosis, viral infection, syphilis, and sarcoidosis. However, these are rare causes of knee pain.

Medication side effects — Systemic glucocorticoids have been linked to osteonecrosis (avascular necrosis of bone), which is discussed separately. Two high-risk groups for osteonecrosis include renal transplant patients and persons with systemic lupus erythematosus. The presenting symptom is insidious unilateral or bilateral knee pain, exacerbated with weight bearing activity [14].

Statin induced myalgias are well known, however, cases of knee pain associated with the use of statins in combination with phosphodiesterase-5 inhibitor have been reported [15]. Fluoroquinolones [16] and retinoids [17] and have been reported to cause knee pain in children and adolescents.

Vaccinations — There are several case reports of new onset rheumatoid arthritis with knee involvement in adults after receiving an anthrax vaccine [18]. In addition, there is a case report of right knee reactive arthritis two days following tetanus vaccination [19].

IMAGING — Diagnostic imaging is used as an adjunct to the history and physical examination when evaluating the adult with knee pain. The suspected clinical diagnoses determine the need for imaging and appropriate study selection. Following acute trauma, imaging typically begins with plain radiographs (image 4). In patients with nontraumatic knee pain associated with an effusion, poor response to a treatment plan, or when the diagnosis is unclear, advanced diagnostic imaging may be useful. (See "Approach to the adult with knee pain likely of musculoskeletal origin", section on 'Imaging in the evaluation of acute knee pain'.)

Magnetic resonance imaging (MRI) is the best imaging technique for diagnosis of soft tissue knee injuries (eg, ligament, meniscus). However, for most causes of knee pain, an MRI is unnecessary to make the correct diagnosis. Radiologic assessment of patients with acute knee pain is reviewed in detail separately. (See "Radiologic evaluation of the acutely painful knee in adults".)

Ultrasound has gained popularity for evaluating musculoskeletal conditions, and it offers many advantages in diagnosing certain knee conditions. Ultrasound permits detailed, real-time, evaluation of the soft tissues, collateral ligaments, and tendons surrounding the knee, and is more sensitive and specific for detecting a knee effusion compared with manual techniques. In addition, ultrasound enables the clinician to perform dynamic evaluation of the knee (ie, visualizing knee structures while the knee joint is manipulated), and to compare findings with the contralateral knee. (See "Musculoskeletal ultrasound of the knee".)

Dual-energy computed tomography (DECT) examination is an emerging imaging modality that can identify urate deposits in articular and periarticular locations and can distinguish urate from calcium deposition. (See "Clinical manifestations and diagnosis of gout", section on 'Imaging'.)

Additional ultrasound resources — Instructional videos demonstrating proper performance of the ultrasound examination of the knee and related pathology can be found at the website of the American Medical Society for Sports Medicine: sports US knee pathology. Registration must be completed to access these videos, but no fee is required.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Knee pain".)

SUMMARY AND RECOMMENDATIONS

●Diagnostic categories and algorithm – The differential diagnosis for knee pain in adults is complex; obtaining a clear history is essential. The following flow chart outlines our approach to diagnosis (algorithm 1). Important elements of the history include whether trauma contributed to the development of knee pain and whether pain increases with activity, and if so what sort of activity. Information from the history helps to distinguish five diagnostic categories:

•Acute knee pain following recent trauma or overuse

•Atraumatic knee pain associated with joint effusion

•Atraumatic knee pain NOT associated with joint effusion

•Referred knee pain

•Uncommon causes of knee pain

Key questions to ask the adult presenting with undifferentiated knee pain are reviewed in the text. (See 'History overview and diagnostic categories' above.)

●Physical examination – The physical examination of any joint includes inspection, palpation, range of motion testing, strength and neurovascular testing, and special maneuvers to assess for specific diagnoses. Special tests are selected based upon the most likely diagnostic category, which is based in turn upon the history. Detection of a knee joint effusion is an important part of the examination. The knee examination is described in detail separately. (See "Physical examination of the knee" and 'Physical examination of the knee' above.)

●Key steps for diagnosis – Important steps for determining the underlying cause of pain include the following:

•Distinguish between acute and chronic pain.

•Distinguish between traumatic and nontraumatic pain.

•Determine whether a joint effusion is present.

•Determine the location of the pain.

Each step is discussed in the text. Once a history and examination are performed, and the steps outlined here are completed, the clinician will have narrowed the differential diagnosis to a small number of potential conditions. (See 'Initial steps to categorizing knee pain' above.)

●Trauma-related causes – Common causes of knee pain following acute, low-energy trauma include the following (table 1):

•Medial or lateral collateral ligament tear

•Anterior cruciate ligament tear

•Meniscus tear

•Patella dislocation or significant subluxation

•Patella tendon tear

•Intra-articular fracture

•Osteochondral defect

Important distinguishing features of these diagnoses are reviewed separately. (See 'Acute knee pain associated with trauma' above.)

●Nontraumatic causes with joint effusion – The differential diagnosis of nontraumatic knee pain associated with an effusion can be narrowed based on the association with activity. Important, common causes of nontraumatic knee pain that increase acutely with activity include articular cartilage injury and osteoarthritis (table 2). (See 'Nontraumatic conditions associated WITH a joint effusion' above.)

Knee pain associated with a joint effusion, despite the absence of any trauma or activity that exacerbates symptoms, is a concerning finding, and indicates the need for a more extensive workup. In addition to a careful history and examination, plain radiographs and knee joint aspiration are often necessary. Important causes of nontraumatic knee pain not associated with activity include crystal arthropathy (eg, gout), infectious (septic) arthritis, disseminated gonococcal infection, and systemic rheumatic disease. (See 'Conditions NOT related to activity' above.)

●Causes not associated with trauma or effusion – For knee pain not associated with acute trauma and without a knee effusion, the first step is often to determine if the pain is exacerbated by activity (table 3). Some conditions may cause localized swelling, or an intermittent effusion, but nearly always this occurs with activity. Ask patients that do not participate in regular physical exercise or labor if something in their day-to-day activity has changed (new job, recent vacation, recent work around the house, etc). The second, crucial step is to pinpoint the location of the pain. (See 'Nontraumatic conditions NOT associated with joint effusion' above.)

•Anterior knee – Causes of anterior knee pain unrelated to acute trauma or a joint effusion include Osgood-Schlatter disease, Hoffa’s fat pad syndrome, quadriceps and patellar tendinopathy, bursitis, plica syndrome, patellofemoral pain, and several conditions affecting the patella (eg, chronic subluxation, stress fracture).

•Medial knee – Causes of medial knee pain unrelated to acute trauma or a joint effusion include degenerative medial meniscal tear, saphenous nerve entrapment, and pes anserine bursitis.

•Lateral knee – Causes of lateral knee pain unrelated to acute trauma or a joint effusion include iliotibial band syndrome and degenerative lateral meniscal tear.

•Posterior knee – Causes of posterior knee pain unrelated to acute trauma or a joint effusion include popliteal artery aneurysm or entrapment, popliteal (Baker's) cyst, and popliteus tendinopathy.

●Uncommon causes – Other, less common causes of knee pain, including bone tumors and referred pain, are discussed briefly in the text. (See 'Bone tumors' above and 'Referred pain' above and 'Other infrequent causes of knee pain' above.)

ACKNOWLEDGMENT — The author and editors acknowledge Ron Anderson, MD, and Bruce Anderson, MD, both of whom contributed to earlier versions of this topic review.