7 Rare Causes of Knee Pain

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Knee Pain Without Injury

Injury, ongoing stress, and aging are the most common causes of knee pain. But what if none apply? One of several rare causes of knee pain may be at work, including benign tumors, fluid buildup, infection, certain types of arthritis and even genetic mutations. Many of these causes have the exact same symptoms but require very different treatments. It’s important to work with your doctor to arrive at an accurate diagnosis so you can not only start easing symptoms, but also prevent long-term damage to your knee joint.

1. Tenosynovial Giant Cell Tumor (TGCT)

TGCTs are non-cancerous tumors that grow around the knee joint. They can cause pain, swelling, and stiffness that affects your mobility and stability. Your knee may lock up at times, accompanied by a popping or creaking sound (crepitus). If you have symptoms of TGCT, talk with your doctor. Left untreated, TGCT can lead to osteoarthritis that may damage your knee joint and the surrounding cartilage and bones permanently. Treatment options can include surgery, radiotherapy, or targeted medication that works in the body on a cellular level to improve symptoms.

2. Synovial Chondromatosis

Like TGCT, synovial chondromatosis is non-cancerous and can also lead to osteoarthritis that causes damage if not treated. Symptoms are similar, too: knee pain, swelling, and difficulty with movement, sometimes with a popping sound. Unlike TGCT, synovial chondromatosis doesn’t involve tumors. It’s a condition that occurs when a membrane of the knee that lubricates the joint–the synovium–produces cartilage nodules that bump into and damage healthy, protective cartilage in the joint space. Depending on the size and volume of the nodules, either non-invasive or traditional surgery may be recommended.

3. Chondrocalcinosis 2 (CCAL2)

CCAL2 is a genetic disorder caused by a mutation in the ANKH gene. The mutated gene carries calcium crystals to the cartilage around the knee joint, which damages it. Symptoms can vary significantly. They may include knee pain, swelling, and impaired mobility like other knee conditions or they may feel more like sudden attacks of pain with redness and a warm feeling. CCAL2 can’t be cured, but many effective treatments are available to ease symptoms. They include procedures to drain fluid from the knee and medicines such as corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).

4. Pigmented Villonodular Synovitis

It’s not yet known what causes pigmented villonodular synovitis (PVNS), and the symptoms are similar to other knee conditions. When you have PVNS, the lining of your knee joint swells and grows, and fluid builds up. Your doctor may test fluid from your knee to diagnose the condition. Symptoms can come and go, so the first step may be resting your knee and taking nonprescription pain relievers. If symptoms are severe and persist over time, your doctor may recommend surgery to remove your knee joint lining. A non-invasive procedure may be an option.

5. Adult Still’s Disease

Adult Still’s disease is a type of inflammatory arthritis that can come with distinct symptoms in addition to knee pain: rash, fever, and sore throat. Your knee joint may also feel achy, and nearby muscles may hurt. It’s not known what causes Adult Still’s disease, but some research points to infection. The condition is usually treated with one or more of these medicines: NSAIDs; steroids; methotrexate; and biologic drugs that target your body’s inflammatory response at the cellular level.

6. Septic Arthritis

Septic arthritis is a joint infection, and the most common type is Staphylococcus aureus (staph). The infection can be caused by an injury such as a cut or animal bite or it can be introduced during surgery–but it’s usually caused by an infection that has traveled from another part of your body like your urinary tract or skin. Septic arthritis is painful, and it may come with swelling, redness, warmth, or fever. Treatment usually includes draining the fluid around the knee joint and taking antibiotics.

7. Reactive Arthritis

Like septic arthritis, reactive arthritis in the knee can also be caused by an infection that has travelled from another part of your body. The most common types are sexually transmitted infections (STIs) and food poisoning. Antibiotics are usually prescribed to cure the infection. Symptoms include pain and swelling, as well as irritation of the genitals or eyes. If you have any symptoms of a rare knee condition, try to write them down and note how long they last. Bring this information to your doctor’s appointment to inform the diagnosis and help speed your time to treatment.


The Orthopedic & Sports Medicine Center of Oregon is an award-winning, board-certified orthopedic group located in downtown Portland Oregon. We utilize both surgical and nonsurgical means to treat musculoskeletal trauma, spine diseases, sports injuries, degenerative diseases, infections, tumors and congenital disorders.

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