CHAPTER 35 Spondyloarthropathies
INTRODUCTION
These disorders frequently manifest initially with back complaints. For example, back complaints are the first symptoms in 75% of patients with ankylosing spondylitis and may be present in 89% of patients with undifferentiated spondyloarthropathy.1,2
DEFINITION AND CLASSIFICATION
The spondyloarthropathies are a cluster of overlapping and interrelated chronic inflammatory rheumatic disorders which include ankylosing spondylitis (often considered the prototype), reactive arthritis, arthritis associated with psoriasis, arthritis associated with Crohn’s disease and ulcerative colitis, Reiter’s syndrome, and undifferentiated spondyloarthropathy.3
These disorders are often referred to as the seronegative spondyloarthropathies, which are considered together since they share clinical, epidemiologic, and imaging features. The spondyloarthropathies usually have a negative rheumatoid factor (seronegativity), association with HLA-B27, familial clustering, predominant axial and peripheral joint involvement, and extra-articular manifestations.4
EPIDEMIOLOGY AND GENETICS
Spondyloarthropathies are a group of diseases heavily influenced by genetic factors, particularly HLA. There is a clinical spectrum of these disorders. Undifferentiated spondyloarthropathy is the most common disorder; with ankylosing spondylitis (AS) being second most common. The estimated incidence is likely more common than previously realized as newer classification systems have been developed. Prevalence of SpA is correlated with the presence of HLA-B27 in a particular population.5,6 Both men and women are affected. In ankylosing spondylitis, males are disproportionally affected in a 3:1 ratio.7 Psoriatic arthritis affects men and women equally.8 Postvenereal Reiter’s syndrome is more common in men, whereas postdysenteric Reiter’s syndrome equally affects men and women.9,10
GENERAL CLINICAL FEATURES
In general, spondyloarthropathies demonstrate the following clinical features:
PATHOLOGY
Enthesopathy
The ‘enthesis’ is the region of insertion of a tendon, ligament, capsule, or fascia into bone. The enthesis is now understood to be a complex structure that extends into the bone and marrow cavity.13 Recent work suggests that the entheseal fibrocartilage is the major target of the immune response and the primary site of the immunopathology.14 The bone marrow demonstrates edema and contains cellular infiltrates. T lymphocytes are abundant in these areas with a preponderance of CD8+ cells.15 Pathologic studies have demonstrated inflammatory infiltration and destruction which affect the whole anulus fibrosus, not just the enthesis of the intervertebral disc.16
Synovitis
Patients with spondyloarthropathy may have peripheral arthritis, typically mono- or oligoarticular, and often affecting one or both knees. Microscopic analysis reveals fibrin, synovial cell proliferation, lymphocytes, and plasma cells in the synovium.17 A more recent hypothesis suggests that bacterial antigens and microorganisms in a susceptible HLA-B27-postitive patient may interact to produce inflammation and arthritis in ankylosing spondylitis.18 It is well established in reactive arthritis that synovial fluid demonstrates bacteria-specific T-cell responses to the bacterium that causes the arthritis.19,20
Sacroiliitis
Studies of the sacroiliac joint reveal evidence of synovitis, osteitis, and enthesitis. Biopsy and autopsy specimens demonstrate pannus formation, myxoid marrow, superficial cartilage destruction, intra-articular fibrous strands, new bone formation, and bony ankylosis. Biopsy samples demonstrate cellular infiltrates of T lymphocytes, with both CD4+ and CD8+ cells.21,22 Contrast-enhanced magnetic resonance imaging (MRI) studies of the sacroiliac joints in inflammatory back pain can demonstrate the following: sacroiliitis is more often bilateral in AS (84%) than in undifferentiated SpA (48%); the dorsocaudal parts of the synovial joint and the bone marrow are the most frequently inflamed structures early in the disease; in contrast, the entheses and ligaments are more commonly involved in later stages.23
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of sacroiliitis is narrow and is summarized in Table 35.1.7
| SPONDYLOARTHROPATHIES | |
Spinal pain and restriction may also be caused by diffuse idiopathic skeletal hyperostosis (DISH). In contrast to SpA, DISH usually presents with later age of onset, normal sedimentation rate, larger and more flowing ligamentous ossifications (syndesmophytes), and the absence of sacroiliitis.24
DIAGNOSIS
Ankylosing spondylitis
The classification criteria for AS were reassessed in 1984 and are referred to as the ‘modified New York criteria for ankylosing spondylitis.’ The criteria include both clinical and radiographic categories.25,26 The three clinical criteria include:
The two radiologic criteria include:
Clinical features
Clinical features of AS are heralded by chronic low back pain and stiffness as the initial symptoms in 75% of patients.27 Often, the symptoms develop spontaneously and progress insidiously. Buttock pain that radiates into the thigh may be erroneously blamed on sciatica. This pain may reflect involvement of the sacroiliac joints.28,29 A history of nocturnal back pain, diurnal variation with prolonged morning stiffness, and improvement with exercise should raise the suspicion of an inflammatory etiology to chronic back pain. A good response to nonsteroidal antiinflammatory drug (NSAID) therapy and an age younger than 40 also increase the likelihood of inflammatory back pain.30 Another, less common presentation of AS may be enthesitis or peripheral arthritis, mono- or oligoarticular.31 The enthesitis may involve the Achilles or plantar tendon insertions. The knee is often involved in the arthritis. These findings are not unique to AS. The differential diagnosis may include Reiter’s syndrome or reactive arthritis.
Physical examination
The earliest physical examination finding is often tenderness in the region of the sacroiliac joints or pain on provocative test maneuvers such as hip hyperextension and sacral compression tests. The two most sensitive maneuvers are pressure over the anterior-superior iliac spines and pressure over the lower half of the sacrum.32 As the disease progresses, physical examination findings will reflect restricted ranges of motion. As an example, reduced chest expansion is measured from maximal exhalation to maximal inhalation at the level of the fourth intercostal space. An expansion of less than 2.5 cm is considered abnormal.27 The restricted motion reflects fusion of the costovertebral joints.
Schober’s test and finger-to-floor test will also become abnormal. The Schober’s test is performed by marking the fifth lumbar vertebra and a point in the midline 10 cm above. The patient is then asked to flex forward maximally while maintaining the knees straight. The distance between the two points exceeds 15 cm in normal individuals.1
Laboratory studies
Laboratory studies in AS are often non-specific. Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein are often elevated, but are not specific for AS and do not necessarily reflect disease activity.33,34 A mild normochromic normocytic anemia may be present. Serologic tests for lupus and rheumatoid arthritis should be negative.
HLA-B27 is present in approximately 90% of Caucasian patients and 50–60% of African-American patients with AS.3 It is present in only 6% of the general population.
Undifferentiated spondyloarthropathy, Reiter’s syndrome, and reactive arthritis
The classification criteria for SpA is based on clinical features, as there are no specific confirmatory blood tests. There are two sets of clinical criteria that have been developed and validated in Europe and are used widely. These are the European Spondyloarthropathy Study Group (ESSG) and the multiple-entry criteria by Bernard Amor.1
The European Spondyloarthropathy Study Group criteria
Indications for the designation of spinal pain as ‘inflammatory’ are:
Indications for the designation of synovitis are:
The ESSG criteria have been evaluated in many studies, including those in Europe, Brazil, and Alaska.35–38
The Amor criteria
The Amor criteria are a series of items which are weighted with a point scoring system.1,39,40
In order to qualify for a diagnosis of spondyloarthropathy, a patient must score a total of at least six from among the list of features detailed in Table 35.2.
Table 35.2 Clinical features scored in the Amor classification
| Feature | Score | |
|---|---|---|
| CLINICAL | ||
| Night pain or morning stiffness of the thoracic or lumbar spine | 1 | |
| Asymmetrical oligoarthritis | 2 | |
| Buttock pain (uni- or bilateral) | 1 or 2 | |
| Sausage-like toe or digit | 2 | |
| Heel pain | 2 | |
| Iritis | 2 | |
| Nongonococcal urethritis or cervicitis within 1 month prior to arthritis | 1 | |
| Acute diarrhea within 1 month prior to arthritis | 1 | |
| Presence or h/o psoriasis, balanitis, inflammatory bowel disease | 2 | |
| RADIOLOGIC | ||
| Sacroiliitis (grade >2 if bilateral; grade >3 if unilateral) | 2 or 3 | |
| GENETIC | ||
| HLA-B27 present and/or family h/o spondyloarthropathy | 2 | |
| RESPONSE TO TREATMENT | ||
| Clear-cut response to NSAIDs | 2 |
Specific diagnoses
Reactive arthritis
Inflammatory arthritides developing after a distant infection are labeled reactive.41 Inciting organisms may be: Chlamydia, Yersinia, Salmonella, Shigella, Campylobacter, Clostridium difficile, Brucella, and Giardia.42 The infection should have occurred within 6 weeks of clinical presentation of the arthritis. The presence of HLA-B27 renders the host susceptible; however, there is an interplay between HLA-B27 and environmental/infectious triggers in the development of reactive arthritis.43
Reiter’s syndrome
Reiter’s syndrome represents one example of reactive arthritis. The classic triad of uveitis, urethritis, and arthritis defines Reiter’s syndrome. The pathogenesis is similar to reactive arthritis since both are triggered by an infectious agent and are more common in those patients with the HLA-B27 gene.44
Not all patients present with all three features of the triad. The American College of Rheumatology requires peripheral arthritis (longer than 1 month’s duration) in association with urethritis or cervicitis.45
Undifferentiated spondyloarthropathy
Among patients who meet ESSG or Amor criteria for spondyloarthropathy, there is a large group that does not fit into the above discrete categories. These patients are labeled as undifferentiated spondyloarthropathy.1 In a recent study from Spain,46 68 patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA) were followed for 2 years. At the end of this period, 75% retained the diagnosis of uSpA; disease remission occurred in 13%; ankylosing spondylitis 10%; and psoriatic arthritis 2%. In addition, a subset of patients with uSpA may be found to have reactive arthritis.47
