Knee Pain Differential Diagnosis: A Comprehensive Guide for Clinicians

Anterior knee pain is a prevalent complaint encountered across various clinical settings, from primary care to specialized sports medicine clinics. Establishing an accurate Knee Pain Differential Diagnosis is crucial due to the broad spectrum of potential underlying conditions. This article provides a detailed overview of the differential diagnoses for anterior knee pain, emphasizing key clinical examination findings and management strategies relevant to automotive repair professionals who may encounter clients describing such symptoms.

Understanding Anterior Knee Pain

Anterior knee pain (AKP) represents a significant musculoskeletal issue, affecting a substantial portion of both athletic and general populations. It is estimated that AKP affects up to 40% of adolescent athletes and over 20% of the general population, leading to a diminished quality of life and considerable economic impact due to lost productivity and healthcare costs. Persistent knee pain can also be associated with mental health concerns like depression, highlighting the multifaceted impact of this condition.

When considering knee pain differential diagnosis, it’s essential to recognize the diverse range of potential etiologies. These can span from common tendinopathies and bursitis to more complex conditions like synovial plica syndrome and even, though less frequent, osseous malignancies or referred pain from other areas. Patient age is a critical factor in narrowing down the differential, as certain conditions are more prevalent in specific age groups. For instance, in younger, skeletally immature individuals, conditions such as Osgood-Schlatter disease, Sinding-Larsson-Johansson syndrome, and juvenile osteochondritis dissecans are particularly relevant. In adults, osteoarthritis becomes a primary consideration, alongside osteochondritis dissecans. Traumatic causes, such as patellar dislocation, are also important, though less common in chronic AKP.

Furthermore, it’s important to consider the differential diagnosis for painless knee buckling or giving way. This symptom can arise from transient patellar malposition or subluxation, a trapped synovial plica, unstable cartilage flaps, or ligamentous or meniscal instabilities. In individuals who have undergone knee surgery, the range of differential diagnoses expands to include post-surgical complications.

Clinical Examination for Knee Pain Differential Diagnosis

A thorough clinical examination is paramount in effectively navigating the knee pain differential diagnosis. The examination should commence with a careful visual inspection, assessing for any misalignment, displacement, or muscle atrophy. Observing the patient’s gait, noting the presence of genu valgum (knock-knees) or genu varum (bowlegs), and evaluating joint laxity and rotational abnormalities can provide valuable diagnostic clues. The Q-angle, which reflects the direction of quadriceps muscle pull, is often assessed, particularly in cases of suspected patellofemoral syndrome. While crepitus (grating sound or sensation) is frequently observed, it is not specific to any single condition and may not always be clinically significant. It’s crucial to always consider referred pain originating from the back, hip, or pelvis as a potential source of anterior knee pain.

Localizing the pain is key, both during dynamic activities and upon palpation for point tenderness. In most cases of anterior knee pain, the pain is broadly categorized as retropatellar (behind the kneecap) or peripatellar (around the kneecap), although conditions like Osgood-Schlatter disease deviate from this pattern, presenting pain more distally at the tibial tubercle. Isolated muscle weakness can be indicative of referred pain or specific AKP etiologies. Numerous specialized physical examination tests can further aid in elucidating specific diagnoses suggested by the initial findings.

Patellofemoral Syndrome (PFS) / Idiopathic Anterior Knee Pain Syndrome

Patellofemoral Syndrome (PFS), also sometimes referred to as idiopathic anterior knee pain syndrome, is a broadly defined condition characterized by pain around or behind the patella. This pain is typically exacerbated by activities that increase compressive forces on the patellofemoral joint. PFS is the most common cause of knee pain, especially in young athletes, but it also frequently affects adults and can be a precursor to patellofemoral osteoarthritis. The incidence of PFS can be as high as 6% in certain populations. The pain associated with PFS is often nonspecific and activity-related, worsening with activities like squatting, stair climbing, jumping, and prolonged sitting – the latter known as the “theater sign.”

The exact etiology of PFS remains incompletely understood, but biomechanical and anatomical factors are believed to play a significant role. Research indicates that imbalances in quadriceps and hamstring muscle control, hamstring tightness, and quadriceps or hamstring weakness are correlated with patellofemoral pain. Emerging evidence also suggests that weakness in hip abductor and extensor muscles can contribute to impaired patellar control, thus exacerbating this pain syndrome. In addition to pain, patients may report symptoms like catching, locking, or giving way of the knee.

Clinical assessment for PFS should include observation for patellar or quadriceps asymmetry, joint effusion, gait abnormalities, and signs of referred pain. Evaluating patellar alignment and muscle atrophy is essential. Assessing patellar glide and tracking, including the J-sign (lateral patellar deviation during knee extension), can further support the diagnosis. Tenderness to palpation may be present at the patellar facets or femoral condyles, but its absence does not rule out PFS. Strength testing of the quadriceps, hip abductors, and hip extensors is important. Functional assessments, such as squats or single-leg presses, can also reveal weakness. Clusters of these physical exam findings have been shown to improve diagnostic accuracy, with reported specificity and sensitivity as high as 93% and 96%, respectively. While PFS is primarily a clinical diagnosis, imaging, such as X-rays, can be helpful to rule out other causes of knee pain and support the diagnosis in some cases. Musculoskeletal ultrasound (US) is increasingly used, and findings like effusions, muscle volume, and tendon thickness variations may be valuable in investigating PFS.

Initial treatment for PFS typically involves rest, nonsteroidal anti-inflammatory drugs (NSAIDs), and physical therapy (PT). Physical therapy focuses on strengthening hip flexors, trunk, and knee muscle groups, which is often necessary for patients to return to higher activity levels. Isolated hip strengthening has shown comparable effectiveness to traditional knee strengthening exercises. Combining hip and knee strengthening in a PT program can lead to sustained clinical improvements even after PT completion. Knee immobilization is generally not recommended, but kinesiotaping might offer some benefit, although evidence is currently limited. Unfortunately, chronic pain persists in a significant proportion of patients (up to 78%) despite rehabilitation, and these individuals may have a higher risk of developing arthritis later in life. Surgery is typically considered only as a last resort for severe, refractory cases.

Clinical Pearls for Patellofemoral Syndrome:

• PFS is a very common cause of knee pain, particularly in adolescents, affecting up to 6% of this population.
• Diagnosis is primarily clinical, based on history and physical examination findings.
• NSAIDs can help manage pain, but physical therapy focusing on hip, trunk, and knee muscle strengthening is the mainstay of treatment to address underlying biomechanical issues.

This is a normal knee X-ray as would be expected with Patellofemoral Syndrome. Case courtesy of Dr Andrew Dixon, Radiopaedia.org. From the case rID: 36689

Juvenile Osteochondritis Dissecans

Juvenile Osteochondritis Dissecans (JOCD) is a condition affecting bone and cartilage in the knee, primarily involving the femoral condyles. Despite its name suggesting cartilage disease, JOCD is characterized by bone delamination and necrosis, rather than primary cartilage injury. The lateral aspect of the medial femoral condyle is the most commonly affected site. JOCD is not exclusive to athletes and can occur in non-athletic individuals as well. If JOCD is suspected, plain radiographs (X-rays) are indicated as they can reveal a lucent (darker) area in the bone indicative of the lesion. MRI can provide more detailed information, particularly for assessing chondral damage and the stability of the lesion, although its routine use in children is debated, and adult criteria may not be directly applicable to pediatric cases. Patients with JOCD often present with anterior or medial knee pain. Physical examination may reveal a small knee effusion, and tenderness to palpation of the femoral condyle is frequently, but not always, present.

If a JOCD lesion is identified, initial management typically involves rest and activity restriction, which often leads to spontaneous healing within 8-12 weeks in children. Resolution is determined by pain relief and radiographic evidence of healing. Spontaneous resolution is more common in children and adolescents than in adults. In severe cases, knee immobilization may be necessary. Surgical intervention is considered for unstable lesions or those that fail to heal with conservative management. Stable lesions that do not show adequate healing after 3-6 months of conservative treatment warrant referral to an orthopedic surgeon for possible surgical intervention.

Clinical Pearls for Juvenile Osteochondritis Dissecans:

• JOCD is a relatively rare condition usually diagnosed via X-ray.
• Rest and activity restriction are the primary treatments, leading to resolution in most pediatric cases.

Case courtesy of Dr. Maulik S. Patel, Radiopaedia.org. From the case rID: 10668

Patellar Tendinopathy

Patellar tendinopathy, often referred to as “jumper’s knee,” is a common overuse injury affecting the patellar tendon. It is particularly prevalent in athletes involved in jumping and high-impact activities. Risk factors include high body mass index (BMI), waist-to-hip ratio, arch height abnormalities, and limited quadriceps and hamstring flexibility. Patients with patellar tendinopathy typically experience activity-related pain and point tenderness over the proximal patellar tendon. Pain is often most pronounced during knee extension and tends to decrease with knee flexion. Assessing for quadriceps and hamstring weakness or tightness can help identify contributing factors and guide rehabilitation strategies focused on strengthening and stretching.

Diagnosis of patellar tendinopathy is primarily based on history and physical examination. If imaging is considered, ultrasound (US) has been shown to be more sensitive than MRI for evaluating patellar tendinopathy. Conservative treatment is recommended for at least six months and includes eccentric squat exercises, which have demonstrated effectiveness in improving symptoms and promoting long-term recovery. During competitive periods when rapid pain relief is needed, isometric exercises may provide temporary pain reduction. Using a patellar tendon strap in conjunction with physical therapy can also be beneficial. Extracorporeal shock wave therapy (ESWT) and platelet-rich plasma (PRP) are treatments with some supporting evidence, but their effectiveness remains inconclusive. Dry needling is another option with moderate evidence supporting its use and minimal associated risks. Surgical management is controversial and generally reserved for chronic, refractory cases where conservative treatments have failed.

Clinical Pearls for Patellar Tendinopathy:

• Clinical history and physical examination are usually sufficient to diagnose patellar tendinopathy.
• Six months of conservative treatment is the initial approach; consider isometric exercises and patellar straps for symptom management.

Quadriceps Tendinopathy

Quadriceps tendinopathy is another common anterior knee tendinopathy, often affecting the quadriceps tendon at its insertion on the proximal patella. The clinical presentation and management are broadly similar to patellar tendinopathy. Patients typically experience pain and tenderness in the distal quadriceps, anterior knee, and proximal patella. Quadriceps weakness during knee extension may be present. Initial treatment includes rest, ice, NSAIDs, and stretching exercises. Temporary activity modification is usually necessary. Similar to patellar tendinopathy, a structured physical therapy program focusing on both stretching and strengthening exercises can significantly improve symptoms.

Clinical Pearls for Quadriceps Tendinopathy:

• Diagnosis is made primarily through history and physical examination.
• Rest, NSAIDs, and stretching are the mainstays of treatment; physical therapy can be very helpful.

Osgood-Schlatter Disease

Osgood-Schlatter disease is a juvenile apophysitis, characterized by inflammation at the tibial tubercle apophysis, the growth plate located just below the kneecap. It is an overuse condition common in active children and adolescents, particularly those involved in sports with repetitive knee extension. The exact mechanism is not fully understood but is likely related to repetitive stress and traction at the apophysis due to quadriceps muscle contractions, leading to inflammation and pain. Patients present with tenderness and pain directly over the tibial tubercle, exacerbated by forceful knee extension. Historically considered more prevalent in males, recent studies suggest no significant sex difference. Diagnosis is typically clinical, based on history and physical examination. X-rays are usually not necessary but may be obtained if there is concern for avulsion fracture or to rule out other conditions in the differential diagnosis. X-rays can demonstrate avulsion if it has occurred. Management is primarily conservative and includes NSAIDs, rest, and ice. Quadriceps and hamstring stretching exercises are crucial and should be incorporated into the routines of young athletes with open physes. Patellar tendon straps can also help reduce pain in some individuals. Osgood-Schlatter disease is generally self-limiting, resolving after the tibial tubercle physis closes. Conservative management is successful in over 90% of cases, but operative intervention may be considered in rare, refractory cases. A prominent tibial tubercle can persist even after resolution of symptoms, which may be a cosmetic concern for some patients. Arthroscopic surgery may be considered for particularly resistant cases.

Clinical Pearls for Osgood-Schlatter Disease:

• Osgood-Schlatter disease is a common condition in young athletes.
• Over 90% of patients respond well to conservative treatment with NSAIDs, rest, ice, and activity modification.

Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org From the case rID: 7511

Sinding-Larsson-Johansson Disease

Sinding-Larsson-Johansson (SLJ) disease is another juvenile apophysitis, similar in pathophysiology to Osgood-Schlatter disease. SLJ disease affects the inferior pole of the patella, specifically the patellar tendon insertion at the inferior patellar growth plate. It results from overuse and excessive stress from quadriceps muscle pull on the apophysis during periods of rapid growth. Patients present with pain at the inferior pole of the patella, particularly with activities that forcefully load the patella in flexion, such as running and jumping. Swelling and limitations in activity or athletic performance are often associated. Plain radiographs can help differentiate SLJ disease from bipartite patella or patellar fracture. Ultrasound (US) has also been shown to be effective in diagnosing SLJ disease. SLJ disease typically has no long-term sequelae, and activity can be continued as tolerated, guided by pain levels. Pain can be persistent and may respond to NSAIDs. Similar to other apophysitides, rest, stretching, and strengthening exercises can help improve symptoms. In some cases, prolonged rest is the most effective treatment. Corticosteroid injections are contraindicated in SLJ disease.

Clinical Pearls for Sinding-Larsson-Johansson Disease:

• SLJ disease is less common than Osgood-Schlatter disease but shares similar pathophysiology.
• Ultrasound can be a useful diagnostic tool.
• Activity modification based on pain tolerance is recommended as there are no long-term consequences.

Case courtesy of Dr. Alan Jossimar Zavala Vargas, Radiopaedia.org. From the case rID: 80636

Knee Bursitis

Knee bursitis involves inflammation of the bursae, fluid-filled sacs that cushion and reduce friction around the knee joint. Inflammation can arise from chronic microtrauma, acute injury, infection, or inflammatory arthritis. The knee contains four major bursae, any of which can be affected and cause pain. Prepatellar bursitis, located in front of the patella, is the most common type and is strongly associated with repetitive kneeling or direct pressure on the anterior knee. Swelling in prepatellar bursitis can be significant enough to limit knee range of motion, and effusion may be clinically apparent or detectable on ultrasound. If infection is suspected as the etiology of bursitis, laboratory investigations may be necessary. Fluid aspiration of the bursa can be performed to rule out infection or crystal-induced inflammation, although this is rarely required. Chronic bursitis can be persistent despite conservative measures like NSAIDs, rest, and ice. Range of motion exercises and stretching should also be incorporated into treatment. Corticosteroid injections into the bursa can effectively relieve symptoms but carry potential risks, especially for superficial bursae, including infection and skin atrophy.

Clinical Pearls for Knee Bursitis:

• Consider prepatellar bursitis in patients with anterior knee pain and a history of repetitive kneeling or anterior knee pressure.
• Chronic bursitis can be challenging to manage with conservative treatment alone; steroid injections can be helpful but are not without risks.

Synovial Plica Syndrome

Synovial plicae are remnants of embryological synovial tissue within the knee joint. They are present in up to 50% of the population and are usually asymptomatic. However, in some individuals, they can become symptomatic, leading to synovial plica syndrome. This condition commonly presents as chronic anterior knee pain accompanied by intermittent “locking” or “catching” sensations in the knee, particularly in adolescents and athletes. Symptoms are often associated with flexion-extension movements. The reason why plicae become symptomatic in some individuals despite their high prevalence is not fully understood. MRI can visualize plicae, although it is not always necessary for diagnosis. Conservative management is the initial approach for most patients and includes analgesics, NSAIDs, and physical therapy. The reported efficacy of conservative treatment varies widely in the literature, ranging from 40% to 87%. Surgical resection of the symptomatic plica is indicated for patients with persistent pain that does not respond to conservative treatment.

Clinical Pearls for Synovial Plica Syndrome:

• Synovial plicae are very common anatomical findings that can occasionally become symptomatic and cause knee problems.
• Response to conservative treatment is variable.

This is an MRI diagnosis and is best appreciated with the full set of images. Case courtesy of Dr. Andrew Dixon, Radiopaedia.org. From the case rID: 41239

Bipartite or Multipartite Patella

Bipartite or multipartite patella is a congenital condition where the patella develops from two or more ossification centers instead of the typical single center. These separate segments are connected by fibrous tissue or cartilage. The incidence is higher in males (approximately 90%) and is typically bilateral, although unilateral cases can occur. Most cases are asymptomatic and discovered incidentally on radiographs. Symptomatic bipartite patella is characterized by localized anterior knee pain and swelling, often triggered by trauma or overuse. X-rays are diagnostic, revealing the incomplete ossification. Conservative management, consisting of rest, activity modification, and NSAIDs, is usually effective, with many patients experiencing symptom relief within three to four weeks. Surgical intervention may be considered in refractory cases, but there is no clear consensus on the optimal surgical approach, and various techniques have been described in the literature.

Clinical Pearls for Bipartite or Multipartite Patella:

• Most cases are asymptomatic and found incidentally, responding well to conservative management if symptomatic.
• Contrary to traditional teaching, the condition is often bilateral.

Case courtesy of Dr. Aditya Shetty, Radiopaedia.org. From the case rID: 27156

Summary of Knee Pain Differential Diagnosis

Anterior knee pain is a common presenting complaint with a broad differential diagnosis. A systematic approach, starting with a detailed history and thorough physical examination, is crucial for accurate diagnosis. While imaging can be a valuable adjunct in certain cases, it is not always necessary, and the diagnosis is often primarily clinical. Conservative management, including rest, NSAIDs, and physical therapy, forms the cornerstone of treatment for most anterior knee pain conditions. Surgical intervention is generally reserved for cases that are unresponsive to conservative measures.

Case Conclusion

In the presented case of the 14-year-old cross-country runner with recurrent anterior knee pain, the clinical presentation, particularly the anterior knee pain exacerbated by prolonged flexion (“theater sign”) in an adolescent athlete, strongly suggests Patellofemoral Syndrome (PFS). The absence of findings suggestive of fracture or other surgical pathologies is reassuring. Referral to physical therapy, focusing on hip and knee strengthening, led to significant symptom improvement, confirming the likely diagnosis of PFS and the effectiveness of targeted conservative management.

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