26-09-2017 | Inflammation | Gallery
Inflammatory arthritides
Rheumatoid arthritis (RA) is an autoimmune erosive inflammatory arthritis of unknown etiology. The triggering event is unclear but blood markers suggesting autoimmune activation include high inflammatory markers and positive antibodies such as rheumatoid factor (RF). RF is positive in around 50–80% of patients with RA depending on the stage of the disease, but the disease may also be ‘seronegative’, ie, negative RF, particularly in early disease. More specific autoantibodies have been described and the anti-citrullinated peptide antibodies are in routine clinical use currently. RA is characterized by synovial proliferation and inflammation. This results in soft tissue swelling due to synovitis or tenosynovitis, new vessel formation in the synovium (neovascularisation), bony erosions, bone marrow edema, cartilage destruction and periarticular osteopenia, which are the pathological hallmarks of RA. Within 3 years of symptom onset 19% of patients have erosions and within 20 years they can occur in up to 80% of patients. Erosions are clearly linked with functional disability.
Diagnosis of rheumatoid arthritis (RA) depends on a combination of factors including more than 6 weeks of tender or swollen joints (a homunculus is a convenient method of documenting tender and swollen joint counts – see image on slide), a raised inflammatory response, and a positive rheumatoid factor or anti-cyclic citrullinated peptide antibody test.
Soft tissue swelling is often the first sign of synovitis and may be secondary to synovial proliferation, effusion, or tenosynovitis. This can be visualised as loss of the fat planes and as fusiform swelling around the joints (see the slide). Soft tissue swelling can be subtle and careful review of the periarticular soft tissues of the same joints is required to identify early changes, ie, assess and compare the periarticular soft tissues at the metacarpophalangeal joints separately from the proximal interphalangeal joints. Osteopenia is an early radiographic change of active disease (see image (b) on slide). Osteopenia is thought to be related to high levels of inflammatory cytokines, particularly tumour necrosis factor-alpha and interleukin (IL)-6 and IL-17. It is one of the first features of rheumatoid arthritis and usually predates erosions.
Erosions and ankylosis are hallmark features of rheumatoid arthritis. As the disease progresses, erosions develop at the intracapsular articular margins (known as ‘marginal erosions’ – as per the slide). This region is an area of exposed bone without articular cartilage where the joint capsule inserts, referred to as the ‘bare area’. A combination of synovial proliferation and invasion (‘pannus’) along with high levels of inflammatory cytokines is thought to contribute to the development of marginal erosions.
Progression of erosions occurs without adequate treatment. With progression, there can be bony collapse followed by destruction and ankylosis most commonly seen in the carpal bones. In the images above note ulnar translocation of the proximal row of carpal bones and large ulnar erosion (arrow).
In anatomical terms, swan neck deformities relate to hyperextension at the proximal interphalangeal joints (PIP) and flexion at the distal interphalangeal joints (DIP), while boutonniere’s is caused by flexion at the PIP and hyperextension at the DIP
In the knee, hip, elbow, and shoulder joints articular cartilage loss is the predominant finding on plain radiography. Soft tissue swelling (either synovitis or effusion) is also a common feature, particularly in the knee with an increased soft tissue density in the suprapatellar pouch or anterior displacement of the patella visible on lateral knee x-ray. Erosions are the hallmark radiological feature of rheumatoid arthritis (RA) and can be found in any large joints including the knee and elbow. Hip joint effusions can be determined on anteroposterior radiographs as a widened distance between the lateral aspect of the acetabulum and the medial femoral head. Often this is asymmetrical and comparison can be made with the unaffected side. Cartilage loss in the hip in patients with RA is usually uniform throughout the joint and results in migration of the femoral head superiorly and medially in the direction of the femoral neck angulation. This can result in the femoral head protruding in to the pelvis: a condition known as acetabular protrusion.
The cervical spine is the most commonly affected part of the spine in rheumatoid arthritis (RA), with up to 70% of patients demonstrating involvement. Patients may have asymptomatic disease. The atlantoaxial joint is most commonly involved. This is the articulation between the C1 vertebral body, known as the atlas, and the C2, the axis. The axis has a large superior process, the odontoid peg, which articulates with the anterior arch of the atlas. Synovium can be found between the odontoid process (also referred to as the dens) and the atlas and between the odontoid process and the transverse ligament.
Magnetic resonance imaging (MRI) has the advantage of being able to determine synovitis, synovial fluid, and bone marrow edema (BME; which may be an indicator of inflammation), all of which can be seen in early disease in addition to erosions, which often occur as the disease progresses. Other imaging modalities cannot determine inflammatory changes within the bone marrow. BME on MRI is defined as a high signal with irregular borders on T2 fat-suppressed or short tau (STIR) images. BME may predict future erosions. Synovitis has been defined by the OMERACT group as post-gadolinium enhancement of the thickened synovial membrane. On T1-weighted images, erosions appear as focal cortical defects of low signal intensity (SI). Synovitis enhances post-gadolinium. On T2 images, synovitis, BME, and synovial fluid have high SI. Active tendon involvement with tenosynovitis also appears high SI. Using dedicated views of the metacarpophalangeal joints (as seen in this slide) with coronal STIR, 3D fat-saturated T1 post-gadolinium, axial T2 Fat-Sat images, the pathological processes of tendinosis, joint effusions, synovitis, tenosynovitis, and BME can be detected. Synovial thickening can be differentiated from effusion. Gadolinium contrast enhancement is often used to better delineate the synovitis; however, recent studies have suggested that with appropriate sequencing, this may not always be necessary.
Ultrasonography has many advantages over other imaging modalities. It is quick, repeatable, relatively inexpensive, enables scanning of multiple joints at the same sitting in real time and, if performed in the rheumatology office, has immediate implications for clinical decision-making. Pathological changes including synovitis, tenosynovitis, synovial effusions, bone erosions, cartilage thinning, and increased synovial vascularity can be readily determined using ultrasound. Greyscale synovitis with effusion and with increased power Doppler signal representing slow flow in small vessels within the synovium along with break in the bony cortex (erosion) is shown in this slide.
Seronegative spondyloarthropathies (SpA) are a group of chronic autoimmune inflammatory joint diseases predominantly affecting the axial skeleton and often accompanied by a peripheral arthritis. This group is composed of ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, juvenile spondyloarthritis, and undifferentiated spondyloarthritis. They are all characterized by sacroiliitis (usually bilateral), enthesitis, peripheral arthritis, and dactylitis. The peripheral arthritis of SpA has been defined by several criteria including, most recently, the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and includes asymmetric peripheral arthritis and/or predominant involvement of the lower limb. Dactylitis, soft tissue inflammation in a digit with resulting ‘sausage shape’, and enthesitis, inflammation at the site of tendon, ligament, or capsule insertion onto bone, are common features. Extra-articular manifestations common to all SpAs include anterior uveitis or conjunctivitis, aphthous ulceration, aortic incompetence, and an HLA-B27 genetic association. Erythema nodosum and pyoderma gangrenosum are skin manifestations particularly associated with the enteropathic peripheral arthritis. Any of the seronegative SpAs can cause anterior chest wall pathology (most commonly seen in SAPHO syndrome). The pathological processes of the peripheral joint involvement include synovitis and enthesitis. A well-described pathological finding in the seronegative SpAs is inflammation around the entheseal complex, which may be associated with new bone formation.
As described on the previous slide, the pathological hallmarks of peripheral involvement of the spondyloarthropathies include synovitis, erosions, enthesitis, new bone formation, and dactylitis. In this slide, the radiograph shows soft tissue swelling at distal interphalangeal joints in a woman with untreated psoriatic arthritis.
Radiographic features of enthesitis include new bone formation, bone erosions, periarticular sclerosis and cysts, and calcification of ligaments and tendons. New bone formation is suggested by enthesophytes and periostitis. Synovitis will appear like a joint effusion as previously described. Dactylitis can be observed as diffuse soft tissue swelling throughout a whole digit.
The site of erosion can help differentiate peripheral joint psoriatic arthritis (PsA; around entheseal insertions and centrally resulting in ‘pencil in cup’) from rheumatoid arthritis (RA; marginal). Synovitis is generally the same between the two inflammatory arthritis conditions, but bone marrow edema may be more prominent and occurs at the bony corners of joints and at the entheseal sites in PsA (as in this slide). Magnetic resonance imaging (MRI) of the peripheral joint may also help to differentiate PsA from RA and from osteoarthritis (OA). Dynamic MRI can also detect increased vascularity compared with RA (this increased vascularity is also seen in biopsy samples of PsA). MRI can clearly depict the enthesitis at the distal interphalangeal joints, which occurs in PsA but not OA. Furthermore, whole body multi-joint MRI can be used to assess the extent of disease in joints and entheses. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) along with Outcome Measures in Rheumatology (OMERACT) have also outlined the utility of MRI in the diagnosis and monitoring of PsA. The psoriatic arthritis magnetic resonance imaging scoring system (PsAMRIS) has been proposed for assessing peripheral arthritis in PsA. It is currently used as a research tool and may be adapted for clinical use in the future. This scoring system includes scoring of synovitis, tenosynovitis, periarticular inflammation, bone marrow edema, erosions, and osteoproliferation.
Ankylosing spondylitis (AS) is a chronic systemic inflammatory disorder strongly associated with the HLA-B27 genotype. It is characterized by male predisposition and the propensity to cause ankylosis particularly in the sacroiliac joints, the facet joints, and the intervertebral discs. Adult males in their second and third decades are most commonly affected with a 3:1 male preponderance. The symptoms are often insidious with chronic low back pain and/or buttock pain and stiffness usually beginning in late adolescence or early adulthood. Symptoms are typically ‘inflammatory’ in nature with morning stiffness, pain worse on inactivity and better with movement or stretching. AS can also present with a large joint oligoarthritis, particularly affecting the hip (usually bilateral) and shoulder. Typically large joints such as the hip, knee, shoulder, and elbow are affected in peripheral AS, with synovitis, effusion, and enthesitis. Plain radiographic features typical of hip, shoulder, and knee joint AS include diffuse cartilage loss (rather than localized as in osteoarthritis), effusion, erosions (as in this slide; particularly on the superolateral humeral head in the shoulder), and significant ankylosis. Patellar tendon enthesitis is also common with bony spurs and irregular bony margins.
Large joint involvement is the most frequent peripheral finding in ankylosing spondylitis with synovitis, bone marrow edema, bursitis, and enthesitis clearly visualised by magnetic resonance imaging particularly of the hip, shoulder, and knee in a symmetric pattern. The arthritis can be erosive or nonerosive, but in both types, bony overgrowth followed by ankylosis is found in end-stage disease. Erosive disease is less frequent and usually causes eccentric erosions in the large joints such as the humeral head.
Reactive arthritis also has the eponymous name of Reiter’s syndrome. This is an inflammatory arthritis that occurs in relation to a preceding gastrointestinal (GI), typically Salmonella, Shigella, Yersinia, Escherichia coli, Clostridium difficile or Campylobacter, or genitourinary (GU), particularly Chlamydia, infection. Chlamydia pneumonia has also recently been added to this list. Aseptic arthritis may develop between 1 week and several months after the antecedent infection. HLA-B27 is a predisposing genetic susceptibility to the development of arthritis following a GU or GI infection, and this genotype may also portend more severe disease with a chronic course. Peripheral arthritis associated with reactive arthritis usually involves the lower limbs. Around 26% of patients with reactive arthritis report swelling or pain in the heel at initial presentation of the disease. This is often due to Achilles tendinosis (widening of the Achilles shadow and obliteration of the normal fat planes), retrocalcaneal bursitis (radiodense shadow displacing the normal fat planes between Achilles tendon and calcaneus, with associated erosion), or plantar fasciitis (calcaneal new bone formation at the plantar aponeurosis insertion). Early in the disease process, soft tissue swelling with dactylitis, periarticular osteoporosis, and linear periostitis along the phalangeal shafts are radiographic features. Other soft tissue findings include joint effusion, bursitis, and tendonitis. Joint space narrowing is typical in the bones of the carpus and tarsus. Entheseal calcification related to the patellar and Achilles tendons is commonly found. As the disease progresses, marginal erosions develop (as in this slide; and as seen in rheumatoid arthritis) as well as erosions associated with overlying bursitis, particularly around the calcaneum along with fluffy periostitis causing bony proliferation (as seen in psoriatic arthritis [PsA]). In reactive arthritis, there is relative sparing of the hands (distal interphalangeal joints in particular) and more frequent axial involvement when compared with PsA.