RADIOLOGIC DIAGNOSIS AND PATHOLOGY OF THE SPONDYLOARTHROPATHIES

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The two leading clinical symptoms of spondyloarthropathy (SpA) patients are inflammatory back pain (IBP)44 and asymmetric peripheral arthritis, predominantly of the lower limbs.28, 60 These typical clinical features are also the basis for criteria for classification5, 60 and diagnosis4 of SpA according to the two most widely studied and evaluated sets of criteria.23, 49

Inflammatory back pain with the typical clinical symptoms of back pain at night and at rest with improvement after exercise, also presenting as alternating buttock pain, is in an early stage of disease mainly caused by sacroiliitis and later by inflammation at different spinal sites. In some patients with SpA, IBP can be caused by enthesitis occurring at different locations of the pelvis, such as the spina iliaca.15, 28 The intensity of IBP differs; it can be very severe, but patients with radiologic evidence of sacroiliitis may also be totally asymptomatic.

Other characteristic features of SpA are preceding urogenital and enteral infections, psoriatic skin lesions, a specific type of gut inflammation similar to Crohn's disease, enthesopathy, dactylitis, acute anterior uveitis, a positive family history, and the striking association with (HLA) human leukocyte antigen B27.28, 60 The term SpA comprises the following diseases, which are differentiated on a clinical basis: ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA) and arthritis in chronic inflammatory bowel disease (AIBD). If IBP or the characteristic pattern of peripheral arthritis in combination with enthesitis or a positive family history is present, and none of these subsets can be diagnosed, patients can, according to the European Spondyloarthropathy Study Group (ESSG) criteria, be classified as having undifferentiated spondyloarthropathy (uSpA), the fifth subcategory of SpAs.28, 60, 175 Overlap, transition, and coexistence of these subsets are typical for the SpAs.28, 60 For example, macroscopic and microscopic gut inflammation has been described in all SpA subsets.3, 10, 107, 119, 120, 121, 122, 147

The overall SpA prevalence in Caucasian populations has recently been estimated at 1.9% in a population of healthy blood donors in Berlin, Germany:31 19 of 140 HLA-B27–positive and 1 of 133 HLA-B27–negative donors were found to have SpA. A similar prevalence has been reported in an Eskimo population.22 Prevalence data on uSpA are limited to date. In the earlier cited blood donor study, uSpA and AS were the two most frequent subgroups.31 Data from our outpatient clinic suggest that uSpA is even the most frequent SpA subgroup, but referral bias cannot be excluded26; however, in the already cited Eskimo study, uSpA was also the most frequent subset among early SpA patients.22

Of practical relevance, a relatively high prevalence of SpA has also been found among patients presenting with the frequent complaints of back pain in primary care settings in the United Kingdom:159 18 of 351 patients with back pain had symptoms suggestive of SpA; two of these patients were classified as having AS, and eight as having uSpA. Thus, 3% to 5%—a significant percentage—of the patients with back pain presenting to a primary care practice can be expected to have SpA.

The anatomic sites predominantly involved in the SpA are peripheral and axial joints and entheses at different locations, including:

The joints centrally involved in the SpA are the sacroiliac joints, which were, therefore, analyzed in more detail in this review. Special reference is also given to spondylitis and spondylodiscitis, which may occur mainly in AS. The latter also occurs in uSpA (M. Bollow and J. Braun, manuscript in preparation, 1998).

In later disease stages of AS, the clinical picture is often characterized by increasing stiffness in the spine caused by ossification and ankylosis of ligaments, discs, joints, and vertebrae leading to pain, disability, and deformity42 in some patients. Recent data from the German Kerndokumentation, a national register of approximately 30,000 patients with rheumatic diseases, 178 suggest that the general burden of illness in AS is, in contrast to previous assumptions, not so different from rheumatoid arthritis (RA).177

An as yet rarely recognized feature of SpA is Sjögren's syndrome. In a cross-sectional study, we have recently found an increased prevalence (7.6%) of Sjögren's syndrome in 105 patients with uSpA or AS; this was especially the case in patients with SpA who were also antinuclear antibodies (ANA) positive.27 Whether this observation reflects an association or just coincidence caused by referral preferences is not clear.

In regard to inflammation and new bone formation as the most outstanding pathologic features of SpA, this review concentrates on AS, ReA, and uSpA and on new imaging techniques for axial and peripheral joints, as well as the entheses, such as magnetic resonance (MR) imaging and ultrasonography, and on established and recent histopathologic findings in sacroiliac joints of patients with SpA.

Section snippets

SACROILIITIS IN SPONDYLOARTHROPATHIES

The sacroiliac joints may be involved in all SpA subsets but mainly and most severely in AS.34 These joints are either unilaterally or bilaterally affected in the SpA, with an intensity ranging from mild to very severe inflammation, resulting in partial or complete ankylosis. Symmetric sacroiliitis was found in 89% of patients with AS and in 67% of patients with chronic ReA and PsA in longstanding disease, respectively;13 however, the kind of sacroiliac joint involvement has often been

SACROILIITIS AND HUMAN LEUKOCYTE ANTIGEN B27

The association of HLA-B27 with sacroiliitis has been demonstrated in a study of 440 HLA-B27–positive patients with rheumatic diseases. Eighty-three percent of these patients had sacroiliitis.89 In addition to HLA-B27, there are three risk factors for the development of sacroiliitis and AS in patients with SpA: ReA, gut inflammation, and psoriasis.

The prognostic impact of HLA-B27 on the course of SpA was recently indicated by several studies. In a Finnish study on 16 patients who were involved

PATHOGENESIS OF SACROILIITIS

Why the sacroiliac joint? The reason for the tissue tropism in SpA is still obscure. The localization of the sacroiliac joint not far from the bowel has led to various reports and hypotheses on the role of gut inflammation in SpA. By an increased permeability of the gut wall due to gut inflammation found in SpA, 107, 119, 120, 121, 122 bacteria can get access to the bloodstream more easily. For ReA-associated bacteria, it is not clear how frequently infections with enterobacteriae or chlamydiae

DIFFERENTIAL DIAGNOSIS OF SACROILIITIS

Sacroiliitis also occurs in other bacterial infections that can be clinically somewhat similar to SpA. The sacroiliac joints can be affected in tuberculosis and brucellosis.28, 84, 132 In these diseases, bacteria are generally thought to be locally present, probably also in the sacroiliac joints, but this has not been demonstrated. In patients with spinal tuberculosis, bacteria have been detected in biopsy specimens.14, 84 Can something about the pathogenesis of sacroiliitis be learned from

IMAGING OF SACROILIITIS

Objective evidence of an advanced degree of sacroiliitis is critical for the diagnosis of AS163 and important for the differentiation between AS and uSpA.28, 60 In early and acute stages of sacroiliitis, the diagnosis can be difficult because conventional imaging has a limited capacity when no bony changes are yet present. In advanced disease, the sacroiliac joints almost disappear from the radiograph as a result of ankylosis, the very characteristic feature of AS.43, 150, 163 The development

IMAGING OF SPINAL INFLAMMATION

There have been several reviews on conventional radiographic techniques of the spine in the past few decades.12, 43, 55, 66, 71, 134 This review touches these aspects only briefly and concentrates on new imaging techniques, such as MR imaging.87 The characteristic radiologic features of AS are given in Table 1.

Although in advanced stages of disease, syndesmophytes easily detected on lateral spinal radiographs are a rather specific feature of AS, they are not part of the diagnostic criteria for

SPONDYLITIS

In contrast to what was just discussed for sacroiliitis, the situation with spondylitis is different because at the time when spondylitis develops, the diagnosis of AS is usually clear; however, few cases have no or little sacroiliac joint involvement.78, 95 No clear data indicate how often pathologic radiographs of the spine irrespective of sacroiliac changes might contribute to the diagnosis of AS.

Definite structural changes of the vertebral bone occur as spondylitis anterior described by

SPONDYLODISCITIS

Spondylodiscitis has mainly been a radiologic diagnosis since the original description by Andersson in 1937.7 In 1978, Dihlmann and Delling56 differentiated an inflammatory form of spondylodiscitis and a noninflammatory type caused by osteoporotic fractures known to occur in patients with AS with increased frequency.51 According to a recent report, spondylodiscitis occurs in 15% of patients with AS.90 Using MR imaging, the authors have observed spondylodiscitis in 12 of 20 patients with SpA and

IMAGING OF OTHER JOINTS IN SPONDYLOARTHROPATHIES

The temporomandibular joints can be severely and symptomatically affected in patients with SpA, mainly in AS. This was recently demonstrated in a study using MR imaging technology.136 The sternoclavicular joints are frequently affected in 50% of the patients with AS and PsA, of interest, in the absence of palmoplantar pustolosis.67 The palmoplantar pustolosis is a characteristic feature of the SAPHO syndrome, 91 which is generally regarded as an entity separate from SpA, but the overlapping

IMAGING OF ENTHESES AND JOINTS BY ULTRASOUND

Enthesopathy is a very characteristic feature of the SpA. In a Finnish study using the established technique of ultrasonography for the detection of enthesitis, 53 50% of the examined SpA patients had signs of inflammation at the entheses, predominantly in the achillean region.103 Of possible relevance to the management of SpA, ultrasound examinations using 7.5-mHz devices can also be performed to detect synovial effusion; Baker cysts; bursitis, and to some degree, also synovitis and cartilage

OSTEOPOROSIS IN ANKYLOSING SPONDYLITIS

It is quite clear now that osteopenia occurs already in early disease stages of AS167 and that osteoporotic fractures have an increased prevalence in AS.51 The reasons for this are probably the local and systemic inflammation in all stages of disease and the immobility mainly in later stages. Corticosteroids are of minor importance because they are rarely useful in patients with AS. Although bone loss occurs mainly in the center of the vertebrae, syndesmophytes grow at the lateral rim, also in

PATHOLOGY OF SPONDYLOARTHROPATHIES

Sacroiliitis, very often the initial feature of AS, always starts in the iliac part of the sacroiliac joint, which is characterized by fibrocartilage (whereas the sacral part consists of hyaline cartilage).15 This knowledge could give clues to antigenic targets involved, but nothing has been reported so far. The only speciality of ilial cartilage was narrow collagen fibrils arranged parallel to the articular surface observed in an earlier study.130 The sacroiliac joint is irregularly shaped,

HISTOLOGIC STUDIES OF SPINAL INFLAMMATION

More than half of the spinal structures of patients with AS become affected in the course of disease; rarely this happens very early. The progression is usually from the lumbar vertebrae upward but is often irregular.62 Histologic studies on spinal inflammation in AS have used autopsy material62 and specimens obtained at spinal fusion operations.1 Involvement of the spinal skeleton in the SpA is characterized mainly by two essential features: (1) inflammation and (2) new bone formation. The

HISTOLOGY AND IMMUNOHISTOLOGY OF COMPUTED TOMOGRAPHY-GUIDED SACROILIAC BIOPSIES

An important advantage of the CT-guided sacroiliac joint biopsy technique30 is that it can be combined with intra-articular corticosteroid therapy32 (see Fig. 6). Using this method, we found infiltrates of mononuclear cells and islands of beginning ossification in the tissue samples (Fig. 10) of patients with very active disease.30 By semiquantitative immunohistology, we found relatively more CD4+ than CD8+ and a high number of CD14+ macrophages in the inflamed sacroiliac joints in a ratio not

IMMUNOHISTOLOGIC FINDINGS IN PERIPHERAL JOINTS IN PATIENTS WITH ANKYLOSING SPONDYLITIS AND REACTIVE ARTHRITIS

If the peripheral joint involvement in AS and RA is compared, a statement is usually made that there is not much difference, both showing lymphocytic infiltrates, pannus formation, and joint destruction, in AS more markedly in the root joints, hips and shoulders; however, some differences exist: in AS, less erosions and more ankylosis are generally found. Rheumatoid granulomas and vasculitis do not occur in AS. In some cases granulation tissue starting in the underlying bone marrow was

ANIMAL MODELS

Three animal models are possibly relevant for human SpA disease: the HLA-B27 transgenic rat model80 and two HLA-B27 transgenic mouse models, HLA-B27 transgenic mice lacking β2 microglobulin96 and ANKENT, a model of ankylosing enthesopathy of peripheral joints.166

In the rat model, HLA-B2705 and human β2 microglobulin genes were introduced in several strains of Lewis rats. Only the males of the susceptible 21-4H strain showed swelling, erythema, and tenderness of the tarsal joints of one or both

SUMMARY

Five different subtypes of spondyloarthropathy (SpA) are now recognized. Clinical and radiologic involvement of the sacroiliac joint is an outstanding feature of the SpA, especially ankylosing spondylitis (AS). In this partly debilitating form of SpA a unique type of inflammatory axial involvement is observed which is characterized by inflammation and new bone formation at different spinal sites. In longstanding disease sacroiliitis, spondylitis and spondylodiscitis are easily recognized by

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      Other frequent comorbidities of SpA are osteoporosis and cardiovascular disease. Sacroiliitis, spondylitis, aseptic spondylodiscitis, and inflammatory involvement of the posterior elements of the spine are the typical inflammatory manifestations in the axial skeleton in axSpA [4], which later lead to new bone formation, such as syndesmophytes and ankylosis. An estimated 15% of patients with established AS may later develop a so-called “bamboo spine” [5].

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    Address reprint requests to Jürgen Braun, MD, Section Rheumatologie, Klinikum Benjamin Franklin FV, Hindenburgdamm 30, 12200 Berlin, Germany, [email protected]

    Dr. Braun and Dr. Sieper are supported by grant of the German Minister of Research and Technology.

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