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Erosive osteoarthritis

INTRODUCTION

Erosive osteoarthritis (EOA) is a form of osteoarthritis, characterized by a greater extent of inflammation than the "traditional" osteoarthritis and the presence of radiographic bone erosions. EOA was first described by Kellgren and Moore (1952), but the term "erosive osteoarthritis" was established in 1966 by Peter and colleagues. Classically, EOA is described as osteoarthritis, which affects the DIP and PIP joints, often associated with synovitis and cyst formation, while others call it "inflammatory osteoarthritis» (Ehrlich, 1972). Most authors, however, consider EOA a variety of classical osteoarthritis, although there are conflicting views on whether it is a particular entity or a phase of nodal OA.

EPIDEMIOLOGY

Frequency

OA of the hands is estimated to affect 70% of those aged over 65 (Van Saase et al, 1989; Hochberg, 1991). EOA is believed to be a relatively uncommon clinical subgroup of osteoarthritis, occurring in 5-15% of patients with symptomatic OA of the hands (Ehrlich, 2001).

Gender

EOA affects mainly postmenopausal women, to a much higher ratio (12:1) than men (Greenspan, 2003). In other studies the percentage of women with EOA is estimated at 80% (Anandarajah et al, 2009) to 91.6% (Punzi et al, 2004).

Age

EOA is mainly observed in people aged 50-55 (Greenspan, 2003; Punzi et al, 2004).

PATHOLOGY / PATHOGENESIS

The increased destruction of cartilage, characteristic manifestation of OA, is secondary to the loss of balance between formation and resorption of cartilage. Evidence of increased degradation of cartilage has arisen from studies that have shown elevated levels of markers of cartilage metabolism in patients with EOA, compared with healthy controls (Silvestri et al, 2004).

The inflammation of the synovial membrane appears to play an important role in the etiology of pain in OA and may be a source of inflammatory cytokines (Benito et al, 2005; Bondeson et al, 2010; Hill et al, 2007). During the inflammatory phase of EOA hyperplasia of the synovial membrane is observed (Peter et al, 1966). Similarly, other researchers (Goldie et al. 1973) have observed chronic inflammatory changes of the synovial membrane of DIP joints in patients with EOA. Synovitis of EOA can be detected by ultrasound and MRI (PICTURE 1d) (Tan et al, 2005; Grainger et al, 2007; Vlychou et al, 2009). The analysis of synovial fluid may show mild inflammatory arthritis (Belhorn et al. 1993)

Osteophyte formation and bone sclerosis is an indication that bony tissue is involved in the process of EOA, while lesions of the lateral ligaments may precede joint involvement in patients with OA of the hands (Tan et al, 2005).

The role of inflammatory cytokines

The role of inflammatory cytokines in the pathophysiology of EOA is not completely understood, but there is indirect evidence that cytokines are involved in the process of joint damage that characterizes EOA.

Patients with EOA have high IL-2 levels compared with patients with OA of the hands without erosions (Punzi et al, 1996).

Other studies have shown an association between EOA and a genomic region which contains the IL-1 beta 5810 single nucleotide polymorphism (IL-1B 5810 SNP) (Stern et al, 2003).

Silvestri et al. (2006) observed an increase in IL-4 receptor in the serum (sIL-R4) in patients with OA, as well as with nodal OA of the hands and OA of the hip and knee, compared with healthy controls. IL-4 induces an anti-inflammatory effect by altering the actions of IL-1 and TNF-a. Therefore, an increase in sIL-4R may be associated with a reduction in the availability of IL-4, thereby contributing to the joint damage in patients with EOA.

The role of adiponectin

Adipose tissue may be the main source of inflammatory cytokines. Adiponectin, a protein hormone secreted by adipose tissue, regulates the metabolism of lipids and glucose, and additionally participates in the inflammatory processes in destructive arthropathy (Ehling et al, 2006).

In patients with EOA, increased levels of adiponectin have been observed compared with patients with non-erosive OA and healthy controls (Filkova et al, 2009), indicating that obesity is associated with OA of small joints of the hands(Cicuttini et al, 1996) .

Genetic factors

OA of the hands, especially when associated with Heberden’s and Bouchard’s nodes, seems to have a genetic basis (Stecher and Hersh, 1944; Kellgren et al, 1963).

In patients with EOA an increase in MZa1-antitrypsin phenotype has been found, compared with a healthy population (Peter et al, 1966), as well as a higher frequency of DRB1 * 011 antigen, compared with patients with nodal OA (Punzi et al, 2004).

CLINICAL MANIFESTATIONS

Typically, EOA usually presents with pain, swelling and warmth of the DIP and PIP joints of the hands. Pain often occurs suddenly and in most cases followed by intermittent inflammatory episodes with progressive destruction of the joints (Anandarajah et al, 2009). EOA is also associated with morning stiffness, which can last up to one hour, resembling inflammatory rheumatic diseases such as rheumatoid arthritis.

Another typical manifestation of EOA is stabbing paresthesia (Belhorn and Hess, 1993).

Typically, EOA is bilateral and symmetric, and the DIP joints are more frequently affected than the PIP joints. Among the DIP joints, the second and third are more commonly affected followed by the fourth and fifth (Punzi et al, 2004).

Besides hands, EOA can affect the toes too (Ehrlich, 1972; McKendry, 1985; Mas and Rotes-Querol, 2007; Anandarajah et al, 2009), as well as, rarely, large joints (Ehrlich, 1972 ; Keats et al, 1981).

The clinical examination often reveals tenderness and the presence of Heberden’s and Bouchard’s nodes. Deformities in the form of subluxation, contracture and ankylosis of the fingers can also be observed. The deterioration of deformities often leads to impaired function of the hands.

Patients with EOA have more intense pain, worse function of the hands and more severe radiographic changes than patients with nodal OA of the hands without radiographic erosions (Patrick et al, 1989).

 

FIGURE 1a. Typical radiographic changes of EOA :  "gull wing" deformity and "saw tooth" erosions

RADIOGRAPHIC FINDINGS

EOA is characterized by the presence of erosions often in conjunction with bone hyperplasia, which can vary in size. The classic radiographic findings consist of central erosions, collapse of subchondral tissue and interosseous bone fusions (Ehrlich, 1972; McKendry, 1985). Joint space narrowing and subchondral sclerosis are often observed in conbination with the above findings. Central erosions and marginal osteophytosis often lead to "gull wing" deformity that is the radiographic hallmark of the disease (Martel et al, 1980) (EIKONA 1a).

Other radiographic findings

  •  "Saw tooth» (type of) erosions (FIGURE 1a), which often result in ankylosis (Greenspan, 2003).
  • Telescoping or "opera glass”  (type of) deformity (Greenspan, 2003; Swezey and Alexander, 1971).
  • Ankylosis in 15% of patients with EOA
  • Soft tissue swelling and joint effusions (Punzi, 2004).

The classic radiographic changes of EOA are observed in the DIP and PIP joints. They have also been described in the feet, knees, hips, shoulders and spine (Belhorn and Hess, 1993; Keats, 1981; Swezey and Alexander, 1971; Utsinger et al, 1978).

ULTRASOUND

Ultrasound is more sensitive than plain radiographs in the detection of bone erosions and has the advantage that it identifies in parallel soft tissue changes of musculoskeletal diseases (Grassi et al, 2001).

 

FIGURE 1b. Extended osteophytosis in a patient with EOA

In erosive OA, high-resolution ultrasound shows central erosions and osteophytes, thickening of the synovium, joint effusion, and tenosynovitis (Grassi et al, 2000; Iagnocco et al, 2005; Vlychou et al, 2009).

 

FIGURE 1c. Interphalangeal erosions of joints of feet in a patient with EOA of the hands and feet.

MAGNETIC RESONANCE IMAGING

High-resolution MRI often shows erosions (Grainger et al, 2007). The marginal erosions  are associated with the presence of edema of the bone marrow and synovial hypertrophy.

 

FIGURE 1d. MRI in a patient with EOA: erosions (interrupted arrow), synovitis (long arrow) and edema of the bone marrow (short arrow)

DIAGNOSIS

The diagnosis of EOA is established by the clinical picture, normal acute phase markers, negative rheumatoid factor and / or anti-CCP and radiographic imaging of erosions (see Table 1).

     TABLE 1. Proposed diagnostic criteria for erosive osteoarthritis

  1. Osteoarthritis of the hands based on the ACR (American College of Rheumatology)
  2. Erosions in at least 2 interphalangeal joints of which one must be a DIP joint
  3. Negative rheumatoid factor and/or negative anti-CCP
  4. Absence of personal or family history of psoriatic arthritis
  5. Absence of history of gout and chondrocalcinosis of the hands
  6. Presence of central subchondral erosions
  7. Normal (or near normal) ESR
  8. Normal (or near normal) CRP

NOTE: The first 2 criteria are necessary for the diagnosis of EOA while the last 3 assist the diagnosis

DIFFERENTIAL DIAGNOSIS

  • Non-erosive osteoarthritis
  • Gout
  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Pseudogout

Osteophytes, Heberden’s and Bouchard’s nodes and joint space narrowing may occur in both EOA and osteoarthritis, but central erosions are characteristic only of EOA. Instability and ankylosis of the interphalangeal joints is observed only in EOA compared with OA.

Compared with the central erosions of EOA, the erosions in RA typically develop at  joint margins and do not lead to the typical  "gull wing" image seen in EOA. This image is created by central erosions in the proximal plate with marginal hyperplasia of the distal plate in the PIP and DIP joints.

In psoriatic arthritis marginal erosions are observed in the proximal plate and marginal periostitis in the distal plate of the DIP joints.

In gout, tophaceous deposits occur and erosions are seen as "protruding corners." This image is not observed in EOA (GreenspanA, 2003; Punzi L e tal, 2004)

TREATMENT

As with OA, treatment of EOA is limited to symptom control.

Non-pharmacological treatment

  • Moist heat
  • Paraffin baths
  • Splints
  • Range of motion exercises

Medications

Analgesics (eg acetaminophen) and NSAIDs usually provide moderate control of symptoms.

Intraarticular cortisone injections

The intraarticular cortisone injections may improve some patients with EOA (Utsinger et al, 1978). However, they only offer temporary relief, are usually painful in the small joints of the hands and do not prevent the development of erosions.

Chondroitin sulfate

Several non-randomized, placebo-controlled studies have reported reduction in pain and inhibition of the radiographic progression of erosions after treatment with chondroitin sulfate (Rovetta et al, 2002; Rovetta et al, 2004; Verbruggen, 2006).

In a randomized, double-blind, placebo-controlled study, out of 119 patients with OA of the hands, 34 were treated with chondroitin sulfate and the remaining 85 received a placebo (Verbruggen et al, 1998). After 3 years, radiographic erosions were observed in 29.4% of patients who received the placebo, compared with 8.8% of those treated with chondroitin sulfate.

DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (DMARDS)

Antimalarials

Some studies have shown that hydroxychloroquine is well tolerated and can improve the inflammatory markers in patients with EOA (Bryant et al, 1995; Punzi et al, 1996). The beneficial effect of hydroxychloroquine in EOA seems to be due to the inhibitory action of lysosomal phospholipase D, IL-1 and IL-2.

In an open randomized pilot study lasting 24 months, 24 patients were treated with 300 mg of clodronate intravenously for 1 week, followed by 100 mg of clodronate intramuscularly for 14 days every 3 months. Furthermore, 14 patients with EOA were treated with hydroxychloroquine 400 mg daily for 30 days and then 200 mg daily for 11 months (Saviola G et al, 2011). Patients treated with clodronate had a significant reduction in the pain and number of tender joints and improved the muscle strength of the hands and the global doctor’s and patient’s assessment. In contrast, hydroxychloroquine had no effect.

Methotrexate - gold per os

Oral methotrexate and gold have been used in several studies for the treatment of EOA, but so far their results have not been announced (Belhorn and Hess, 1993). However, none of these agents can inhibit the development of radiographic erosions.

BIOLOGICAL AGENTS

Some biological agents have been used in the treatment of EOA, since, as mentioned, IL-1 and TNF-a play an important role in the pathogenesis of OA (Kobayashi et al, 2005).

Anakinra

Three patients with severe EOA who were treated with anakinra had improvement of pain and global patient’s assessment and discontinued NSAIDs (Bacconnier et al, 2009).

Infliximab

In a pilot study, 10 patients with EOA received intraarticular infusions of infliximab into the PIP and DIP joints compared to saline injections (Fioravanti et al, 2009). After 12 months the patients who were treated with infliximab had a significant reduction in pain and sensitivity, as well as reduction in radiographic score, but without any statistical significance.

Adalimumab

In an open labeled study, 12 patients with moderate to severe EOA were treated with adalimumab 40 mg every second week for 12 weeks. All had 2 or more sensitive or swollen joints and 1 or more erosions in the PIP or DIP joints (Magnano et al, 2007). After 12 weeks only 1 patient responded to ACR 20 (ie only improvement of the number of swollen joints).

In a recent double-blind, randomized study with 60 patients with EOA, adalimumab significantly inhibited the progression of joint damage compared with a placebo (Ghent University Score System; GUSSTM) (3.7%, compared to 14.5%) (P = 0.009) (Verbruggen G et al, 2011).

LAST UPDATED 20/7/12

English translation Natalie Maisi, Medical Doctor

 



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