Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory condition where the body’s immune system attacks the joints and causes inflammation of the joint lining (synovium).. Typically RA is a symmetrical polyarthritis, affecting multiple small joints of the hands and feet bilaterally, and more than 90% of RA patients develop symptoms in the foot and ankle over time.
Structure and function
Diarthrodial joints (the type found between the bones of the feet, among others) are lined by the synovium, which produces a fluid to lubricate the joint and reduce friction and to absorb shock. Synovial tissue has monolayer of cells it containing monocyte-derived cells that remove debris, cells that produce hyaluronic acid, and fibroblasts that produce lubricin.
Pathophysiology of rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease of the synovium, often affecting the small joints of the hands and feet (MCP, PIP, DIP joints). The etiology of RA is likelyt an interplay of genetics, environmental triggers, and immune response leading to an autoimmune attack on the body’s own tissue. In brief, the synovial membrane is infiltrated by macrophages, lymphocytes, plasma cells, and granulocytes. Macrophages secrete matrix metalloproteinases and other proteolytic enzymes that damage the synovial tissue. Plasma cells release Rheumatoid factor (RF) and other immunoglobulins perpetuate the inflammatory response.
A typical patient will likely be female, aged 40 to 60 presenting with pain, stiffness, swelling, and limited range of motion in the joints, prototypically those of the wrists and hands. Initial involvement in the feet occurs in 15% of cases. The stiffness seen in RA is most often worst in the morning, and may last one or two hours. The morning stiffness is due to a build-up of extracellular fluid in and around the joint. Other signs and symptoms are systemic and include loss of energy and appetite, dry eyes and fever. A dry mouth and firm lumps beneath the skin (so-called rheumatoid nodules) may be seen.
In the lower extremity, RA more commonly affects the forefoot; the midtarsal joints are next most likely involved. The forefoot is involved twice as often as the hindfoot.
The changes that occur to the forefoot in patients with RA span a combination of bunions, claw toes, and metatarsalgia. Hallux valgus can be quite severe and the big toe commonly crosses over the second toe. Calluses can also form on the ball of the foot when midfoot bones are pushed down from joint dislocations in the toes. As a result, ulcers can form from the abnormal pressure.
In the midfoot RA weakens the ligaments that support the midfoot causing collapse of the arch. Bony prominences can appear on the arch. Rupture of the tibialis posterior tendon can occur, and if it does, the talonavicular joint and subtalar joints sublux and the hindfoot drifts into valgus, leading to midfoot hyperpronation.
Radiographs may show soft tissue swelling, subchondral bone erosions, osteopenia, joint space narrowing, bony destruction, and the classic finding of peri-articular erosions. Osteopenia starts in the metaphyseal region underlying collateral ligament attachments and becomes more generalized as the disease progresses. Cartilage destruction produces narrowing of the joint. Mal-alignment, displacement, and ankylosis of the joint mark end-stage rheumatoid disease.
Synovial fluid: Aspiration and analysis of the synovial fluid is important for distinguishing RA from non-inflammatory and infectious arthrosis. The fluid in patients with RA will be sterile, with increased neutrophils and increased protein but decreased viscosity.
RA is the most common of the inflammatory arthritides affecting about 1% of people, with female: male ratio of 3:1. The peak incidence is at age 50, and symptoms most commonly develop between age 40 to 60.
RA of the foot can present with findings that may suggest other conditions, as follows:
- Crystal induced arthritis (gout/pseudogout): usually involves the knee, the metatarsal-phalangeal joint of the big toe, and the heel, and can be diagnosed with an aspiration of the joint fluid.
- Osteoarthritis: usually seen in older patients and affects weight-bearing joints asymmetrically. Pain worsens with prolonged use of the joint. Can be distinguished with x-rays.
- Systemic lupus erythematosus: characterized by the “butterfly rash” on the face, photosensitivity, joint pain in the hands and feet, and presence of antibodies against double-stranded DNA
- Scleroderma: joint inflammation, compression syndromes (carpal tunnel is often an initial symptom of scleroderma)
- Psoriatic arthritis: distinguished by nail and skin changes
- Lyme disease: check patient’s history of presence in endemic regions and order appropriate blood tests as necessary to diagnose.
- Reiter’s syndrome (reactive arthritis): asymmetrically involves the heel, sacroiliac joints, and large joints of the leg. Also associated with urethritis, conjunctivitis, iritis and painless buccal ulcers.
- Ankylosing spondylitis: though this involves the spine, it’s possible that RA-like symmetrical, small-joint polyarthritis might also occur in AS.
- Hepatitis C: may induce Rheumatoid factor auto-antibodies, and can cause RA-like symmetrical small-joint polyarthritis
- Acute rheumatic fever: migratory pattern of joint involvement (usually asymmetric), with history of antecedent streptococcal infection
- Gonococcal arthritis: migratory pattern involving tendons around ankles and wrists, with history of antecedent gonococcal infection.
RA can be systemic. Consider the diagnosis of RA as a red flag to prompt an evaluation of for problems elsewhere. RA is a systemic disease that affects blood vessels, nerves, and tendons throughout the body. Patients with extra-articular manifestation are more likely to have a high RF titer, more severe disability, and increased mortality rate.
Treatment options and outcomes
There is currently no cure for RA; medical treatments focus on controlling the disease and preventing progressive loss of function of the joints.
NSAIDs and corticosteroids (oral or injections) are used to alleviate inflammation and vasculitis. There are now a series of disease modifying anti-rheumatic drugs (DMARDs) that slow progression and improve symptoms, function, and quality of life. Common DMARDs include Methotrexat and biologic agents such as etanercept, infliximab and adalimumab that offer a more specific approach by targeting the pro-inflammatory cytokine TNF
In the case of flare ups of the foot and ankle, considerable relief can be gained from the use of appropriate footwear and insoles. Stiff soled comfort shoes with a soft accommodative orthotic and a wide toe box can be very helpful in patients with RA. An orthotic and/or a rocker soled shoe can support RA involvement of the midfoot (arch) and ankle. Some patients may benefit from the use of ankle bracing or even use of a removable walking cast boot.
In cases of midfoot hyperpronation, fusion of the talonavicular joint using an iliac bone graft can provide the foot with a stable medial beam and prevent the calcaneus from taking a fixed valgus position. Elhar et al (PMID: 980422) recommends considering fusion at the earliest signs of midfoot hyperpronation in order to minimize the risk of non-union, which can be relatively high in RA patients.
When RA affects the posterior tibial tendon, early synovectomy of the tendon sheath relieves discomfort and can delay or prevent rupture. When posterior tibial tendon rupture has occurred, transfer of the flexor digitorum longus tendon to the distal posterior tibial tendon stump combined with a subtalar fusion or a medializing calcaneal osteotomy may be necessary.
If RA of the forefoot has severely progressed, one option is the Hoffman procedure which is an intense procedure that removes all of the metatarsal heads in the foot. This removes the bony ends and shifts the weight-bearing surface to the bottom of the foot. This MTP joint sacrificing procedure should be performed only in advanced disease, as it is quite destructive and non-anatomic.
Another procedure for advanced cases is triple arthrodesis, which fuses the talonavicular, subtalar, and calcaneocuboid joints. Fusion improves stability of the hindfoot and allows for easier weight-bearing. A potential complication is that other joints of the foot later develop arthritis as they will accept more stress after a triple arthrodesis.
Risk factors and prevention
Risk factors include HLA-DR4 haplotype; female gender; smoking history; and periodontal disease. While alone it has not been associated with increased risk of developing RA, obesity has been linked to poorer prognosis and response to treatment modalities, as reported by Rodrigues et al (PMID: 24489135).
Synovium is partially derived from the word ovum, Latin for egg, because of the yolk-like consistency of synovial fluid.
Synovitis, morning stiffness, rheumatoid factor, ACPA, HLA-DR4, symmetrical polyarthritis, claw toes
How to recognize RA and distinguish it from osteoarthritis
How to analyze synovial fluid and distinguish inflammatory vs non-inflammatory, and infectious vs non-infectious arthritides.
How to assess joint damage in radiographs
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