The seronegative spondyloarthropathies comprise a group of non-rheumatoid disorders with similar clinical, laboratory and genetic features. Recognition of new clinical features has supported the notion that they all form part of a clinical spectrum. These features and the classification of the seronegative spondyloarthropathies are discussed in the review.peer-reviewe

Borg, Andrew A.

Dawes, Peter T.

Hothersall, T.E.

English

OAR@UM

Maltese Medical Journal 20 Volume V Issue I 1993 SERONEGATIVE SPONDYLOARTHROPATHIES · A REVIEW PART I: CLASSIFICATION AND DIFFERENTIAL DIAGNOSIS BORG AA MD MRCP, RESEARCH REGISTRAR DAWES P.T. MB BS MRCP, CONSULTANT RHEUMATOLOGIST HOTHERSALL T.E. MB CHB FRCPE FRCP, DIRECTOR, STAFFORDSHIRE RHEUMATOLOGY CENTRE STAFFORDSHIRE RHEUMATOLOGY CENTRE STOKE-ON-TRENT UNITED KINGDOM ABSTRACT The seronegative spondyloarthropathies comprise a group ofnon-rheumatoid disorders with similar clini­cal, laboratory and genetic features. Recognition of new clinical features has supported the notion that they all form part of a clinical spectrum. These features and the classification of the seronegative spondyloarthropathies are discussed in the review. The seronegative spondyloarthropathies consist of a group of non-rheumatoid disorders with similar clinical, laboratory and gcnetie features. Several of these disor­ders have salient characteristics that enable full recogni­tion of the individual syndrome. It is not invariably possible to make a clear distinction between the various clinical entities, lending support to the notion that they should be considered as part of a clinical spectrum [1]. These disorders [21 are characterised by (Table 1) 1. Absence of high titre IgM rheumatoid factor. High titres of rheumatoid factor have been correlated with severe progressive rheumatoid arthritis (RA), but low titres are found in many connective tissue diseases, chronic infections and 5% of normal individuals. The frequency of rheumatoid factor increases with age [31. 2. Sacroiliitis and/or spinal involvement. The hallmark of ankylosing spondylitis (AS) is bilateral, symmetric sacroiliitis. An asymmetric or unilateral dis­tribution may be evident in the early disease phase. In patients with psoriatic arthritis or Reiter's disease, the pattern of sacroiliitis is most often bilateral and symmet­ric, but asymmetric or unilateral involvement is seen more often than in AS. In the spine, AS may result in abnonllalities of the discovertebral junction, the apophyseal and costovertebral joints, posterior and anterior ligaments and the atlanto­axial articulations. Changes are usually first seen at the thoracolumbar junction. Osteitis at the discovertebral junction, occurring centrally or at the vertebral corners, is an important early sign of AS. Erosion of the vertebral edges creates a squared contour and with healing, reac­tive sclerosis results. Studies of the relationship between sacroiliitis and as­cending spinal disease suggest that these conditions form parI of the same disease spectrum with progression from onc to the other depending mainly on disease duration. TABLE I Characteristics of the Spondyloarthropathies 1. Absence of high-titre IgM Rheumatoid Factor. 2. Sacroiliitis/Spinal involvement. 3. Peripheral inflammatory arthropathy. 4. Familial aggregation. 5. Extra-articular involvement. 6. Enthesopathy. Psoriatic spondylitis and Reiter's disease produce iden­tical findings in the spine. In Reiter's disease however, the incidence and extent of spinal disease is often less than in psoriatic spondylitis or AS. Vertebral squaring anddiscovertebral osteitis are relatively uncommon find­ings in psoriatic and Reiter's spondylitis. Spinal changes classically involve the lower thoracic and upper lumbar segments and segmental spinal involvement is common [4]. Although AS is historically regarded as a male disease, it is increasingly being recognised in females. There does not appear to be any difference in the spinal symptoms, chest expansion, peripheral arthritis and extra-articular features between males and females with AS (Figure 1). Maltese Medical Journal 21 Volume V Issue I 1993 FIG. I Classical appearance ofa male patient with AS. Note the marked kyphosis. Although males tend to have more severe axial disease and more pronounced radiological changes at an earlier stage than women, the overall pattern of clinical disease is similar in both sexes [5-7 J. Chest pain aggravated by coughing or sneezing due to involvement ofcostovertebral and costotransverse joints is now recognised to be a feature of AS and may be present in up to 63% of patients. The chest pain has been shown to predate the diagnosis of AS in 18% of patients and is often associated with tenderness over the sternocostal or costochondral junction [8J. A disorder that may present with similar spinal changes is Diffuse Idiopathic Skeletal Hyperostosis (DISH). This disorder is characterised by the formation of large osteophytes and enthesopathy. It is generally seen in patients over the age of 50. Patients may be asympto­matic or complain of back stiffness. The radiographic criteria for diagnosis require the ab­sence of extensive degenerative disc disease or inflam­matory changes in the sacroiliac and apophyseal joints (Figure 2). A characteristic extraspinal manifestation of DISH is extensive enthesopathy with prominent calcifi­cation and ossification of tendons and ligaments [9 J. 3. Peripheral inflammatory arthropathy Involvement of peripheral joints in AS is often mild and transient. The most common extra-axial joints involved are the hip and the glenohumeral joint. Prominent ero­sive and destructive changes may occur and the hip, in particular, may be an important source ofclinical disabil­ity. Radiographic findings include osteophytosis, subchondral cysts and concentric joint space narrowing [lOJ. Psoriatic arthritis demonstrates a wide variety ofpatterns of peripheral joint disease. These include an asymmetric oligoarthritis (70% ofcases), a symmetrical polyarthritis similar to RA (15 %), predominant distal interphalangeal involvement «5%) and a mutilating arthritis «5%). In less than 5% of patients with psoriatic arthritis, AS is the predominant feature. This classification has been challenged, the main argu­ment concerning the pattern of the peripheral arthritis found. A recent study [11 J suggests that the majority of subjects with psoriatic peripheral arthritis have a sym­metrical polyarthritis resembling that of RA and most present with this pattern of disease. Fusion of the interphalangeal joints is a useful marker of psoriatic arthritis, as this is rarely seen in AS, Reiter's disease or RA. The peripheral arthritis of psoriasis may result in a radiographic appearance similar to that of inflammatory (erosive) osteoarthritis. This disorder is commonly seen in elderly women and tends to involve the DIP and PIP joints, and is associated with central, rather than marginal, erosions in combina­tion with osteophyte formation. Periarticular osteoporosis is usually absent and bony anky losis ofthe interphalangeal joints occurs [12]. The peripheral arthritis of Reiter's diseaseIReactive ar­thritis is characterised by asymmetric involvement ofthe FIG. 11 Plain X-ray of early Forrestier's disease show­ing large osteophytes with normal sacro-iliac joints. Maltese Medical Journal 24 Volume V Issue I 1993 axial or large weight-bearing joints. The knees and ankles are most often involved. Spondylosis with promi­nent enthesitis is often a feature. Radiographic findings are similar to those of psoriatic arthritis, however, sig­nificant destruction or deformity and bony ankylosis is less than in psoriatic arthritis. There is also less cervical spine and upper extremity involvement. 4. Familial aggregation The occurrence of AS has been recognised in twins, brothers, fathers, mothers, and otherrelatives ofaffected individuals [13]. The different disease expressions of relatives of patients with AS, Psoriatic arthritis or Reiter's disease is also well recognised, and considered in greater detail later. 5. Extra-articular involvement: Iritis and conjunctivitis Urethritis Mucous membrane ulcers Skin rash Cardiovascular involvement in the form of myocardial dysfunction, cardiac valvular lesions and conduction disturbances is being increasingly recognised in AS and the related spondyloarthropathies [14-16]. 6. Enthesopathy (Figure 3) This is defined as inflammation at the ligament-bone junction [17]. Favoured sites of involvement include the ischial tuberosities, iliac crests, femoral trochanters and plantar aspect of the calcaneus. Inflammation results in subtendinous/subligamentous erosion, which is followed by reactive sclerosis and heterotopic ossification [18]. The clinical entitles included in the seronegative spondyloarthropathy group are [19]: 1. 	 Ankylosing Spondylitis 2. 	 Psoriatic Arthropathy 3. 	 Reiter's Disease/Reactive Arthritis ENTHESITIS INFLAMMATORY ZONE TENDON/ -LlGAMENT/ -JOINT CAPSULE --­FIG. III Diagram illustrating the definition ofan enthesis. 4. 	 Inflammatory Bowel Disease (Ulcerative colitis, Crohn's disease, Whipple's disease) 5. 	 Juvenile Chronic Arthritis (JCA). JCA is defined as the occurrence of inflammatory arthri­tis before the age of sixteen [20]. The existence of several clinical forms of JCA is well recognised [21]. Pauciarticularand polyarticular JCAare immunologically distinct with persistent pauciarticular disease develop­ing preferentially in patients having HLA-DRw8 while in the polyarticularformofJCA HLA-DPw3 is the major factor for susceptibility [22]. Polyarticular JCA has a clinical spectrum similar to adult RA. Systemic onset JCA is characterised by fever, an evanescent rash, variable arthritis and a marked acute phase response. Pauciartiuclar JCA has a clinical presentation similar to the seronegative spondyloarthropathies with lower limb arthritis, enthesitis, acute uveitis and eventual sacro­iliitis in a number of cases [23]. The classification of Behcet's Syndrome (BS) is still controversial. Some groups still suggest that it should be grouped with the seronegative spondyloarthropathies because of its involvement of mucous membrances, eyes, gastro-intestinal and genito-urinary tracts, and joints. However, in view of the clear difference in these lesions as well as the different HLA spectrum, the current thinking is that BS should be classified with the vasculitides. This is in keeping with the histological finding of both arterial and venous vasculitis [24]. The term "Reactive Arthritis" was introduced by Ahvonen in 1969, and can be defined as a "Syndrome character­ised by nonpurulent joint inflammation following an infection elsewhere in the body" [25]. Epidemiological evidence accumulated from different sources strongly favours a casual relationship between gastro-intestinal infections with Shigella, Salmonella, Yersinia, Campylobacter and genito-urinary infection with Chlamydia and the subsequent development of arthritis. Most patients with reactive arthritis are young adults, aged 20-40 years [26]. The arthritis usually appears up to three weeks following the onset of infectious symptoms. The initial infection is often mild and may be asympto­matic in about 10% of patients [271. The severity of the triggering infection does not bear any clear correlation with the development of arthritis. Sexu­ally acquired reactive arthritis usually follows urethritis or cervicitis but the triggering infection cannot always be identified [28]. In women, urogenital involvement may precede joint symptoms by up. to five years [29 j. The time lag between infection and the onset of arthritis is the main difficulty in identifying the aetiology of the triggering infection. Maltese Medical Journal 25 Volume V Issue I 1993 By the time the diagnosis is suspected, microbiological culture, whether in urine, blood or stool is usually negative. Thus, the diagnosis is usually serological [30]. References l. 	 Espinoza LR, Aguilar JL, Gutierrez F. Infections in the seronegative spondyloarthropathies. Curr Op Rheumatol 1989; 1:151-158. 2. 	 Calin A. Spondyloarthropathies: an overview. In: Spondyloarthropathies; 1984; Ed. Calin A. ; Grune and Stratton, Orlando. pl-3. 3. 	 Wolfe F, Cathey MA, Roberts FK. The latex test revisited. Arthritis Rheum 1991 ; 34: 951­960. 4. 	 Bywaters EGL, Dixon ASJ. Paravertebral ossification in psoriatic arthritis. Ann Rheum Dis 1965; 24:313. 5. 	 Braunstein EM, Martel W, Moidel R. Ankylosingspondylitis in men and women: a clinical and radiographic comparison. Radiology 1982; 144:91-95. 6. 	 Marks SH, Barnett M, Calin A. Ankylosing spondylitis in women and men: a case-control study. J Rheumatol1983; 10:4-9. 7. 	 Resnick D, Dwosh IL, Goergen TG, et al. Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women. Radiology 1976; 119:293-297. 8. 	 Dawes PT, Sheeran TP, Hothersall TE. Chest pain - a common feature of ankylosing spondylitis. Postgrad Med J 1988; 64:27-29. 9. 	 Kerr R. Radiology of the seronegative spondyloarthropathies. Clin Exp. Rheum 1987; 5jS-1: 101-104. 10. 	 Moll JMH, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973; 3:55-78. 11. 	 Helliwell P, Marchesoni A, Peters M, Barker M, Wright V. A re-evaluation of the osteoarticular manifestations of psoriasis. Br J Rheum 1991; 30:339-345. 12. Martel W, Stuck KJ, Dworin AM, Hylland RG. Erosive osteoarthritis and psoriatic arthritis: a radiologic comparison in the hand, wrist and foot. Am J Radiol 1980; 134: 125-130. 13. 	 Graham W, Uchida lA. Heredity in ankylosing spondylitis. Ann Rheum Dis 1957; 16:334-340. 14. Bergfeldt L, Insulander P, Lindblom D, Moller E, Edhag O. HLA-B27: an important genetic risk factor for lone aortic. regurgitation and severe conduction system abnormalities. Am J Med 1988; 85:12-18. 15. 	 Nagyhegyi G, Nadas I, Banyai F, et al. Cardiac and cardiopulmonary disorders in patients with ankylosing spondylitis and rheumatoid arthritis. Clin Exp Rheumatoll988; 6:17-26. 16. Shetty HGM, Fraser AG, Phillips mw,Lazarus JH, Williams BD. Carotid sinus hypersensitivity and complete heart block in Reiter's syndrome. Br J Rheum 1988; 27:321-323. 17. 	 Moll JMH. Pathogenetic mechanisms in B27 associated diseases. Br J Rheum 1983; 22 (Suppl 2):93. 18. 	 Resnick D, Reiter's syndrome. In: Resnick D, Niwayama G. Eds. Diagnosis of Bone and Joint Disorders. Philadelphia, WB Saunders Company, 1981 , p.1134. 19. 	 Moll JMH, Haslock I, Wright V. Seronegative spondyloarthropathies. In: Copeman's textbook of the Rheumatic diseases 1986, Vol. 1, 6th ed.; Ed. Scott JT. ; Churchill Livingstone, London. p723-744. 20. 	 Munthe E. The care of Rheumatic Children. EULAR Bulletin 1977; 47-50. 2l. 	 Schaller JG. Chronic arthritis in children: juvenile rheumatoid arthritis. Clin Orthop 1984; 182: 79-89. 22. 	 Fernandez-Vina MA, Fink CW, Stastny P. HLA antigens in Juvenile arthritis. Arthr Rheum 1990; 33:1787-94. 23. Holt PJL. The classification of Juvenile Chronic Arthritis. Clin Exp Rheum 1990; 8:331-333. 24. 	 International Study Group for Behcet's Disease. Criteria for diagnosis of Behcet's disease. Lancet 1990; 335:1078-1080. 25. 	 Ahvonen P, Sievers K, Aho K. Arthritis associated with Yersinia enterocolitica infection. Acta Rheum Scand 1969; 15:232­253. 26. 	 Kalliomaki JL, Leino R. Follow-up studies of joint complications in Yersinosis. Acta Med Scand 1979; 205:521-5. 27. 	 Ahvonen P. Human Yersinosis in Finland. 11. Clincial features. Ann Clin Res 1972; 4:39-45. 28. 	 Csonka GW. Long-term follow-up and prognosis of Reiter's syndrome. Ann Rheum Dis 1979; 38 (Suppl 1): 24 29. 	 Yli-Kerttula U. Reiter's syndrome or uro­arthritis in females with special emphasis on chlamydial infections. Thesis, Acta Univ Tamperensis 1984; 177: 18l. 30. 	 Lahesmaa-Rantala R, Toivanen A, Clinical spectrum of reactive arthritis. In: Toivanen A Ed. Reactive Arthritis. CRC Press, 1988, 3-7. The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. Users may access this full-text article and can make use of the information contained in accordance with the Copyright Act provided that the author must be properly acknowledged.  Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. This article has been reproduced with the authorization of the editor of the Malta Medical Journal (Ref. No 000001)  

A re-evaluation of the osteoarticular manifestations of psoriasis.

Arthritis associated with Yersinia enterocolitica infection. Acta Rheum Scand

Cardiac and cardiopulmonary disorders in patients with ankylosing spondylitis and rheumatoid arthritis. Clin Exp Rheumatoll988;

Carotid sinus hypersensitivity and complete heart block in Reiter's syndrome.

Clinical spectrum of reactive arthritis. In: Toivanen A Ed. Reactive Arthritis.

Erosive osteoarthritis and psoriatic arthritis: a radiologic comparison in the hand, wrist and foot.

Follow-up studies of joint complications in Yersinosis. Acta Med Scand

Group for Behcet's Disease. Criteria for diagnosis of Behcet's disease. Lancet

Heredity in ankylosing spondylitis. Ann Rheum Dis

HLA antigens in Juvenile arthritis. Arthr Rheum

HLA-B27: an important genetic risk factor for lone aortic. regurgitation and severe conduction system abnormalities.

Human Yersinosis in Finland. 11. Clincial features. Ann Clin Res

Long-term follow-up and prognosis of Reiter's syndrome. Ann Rheum Dis

Pathogenetic mechanisms in B27 associated diseases.

Psoriatic arthritis. Semin Arthritis Rheum

Radiology of the seronegative spondyloarthropathies. Clin Exp. Rheum

Reiter's syndrome or uro arthritis in females with special emphasis on chlamydial infections. Thesis, Acta Univ Tamperensis

Seronegative spondyloarthropathies. In:

The care of Rheumatic Children. EULAR Bulletin 1977; 47-50. 2l. Schaller JG. Chronic arthritis in children: juvenile rheumatoid arthritis. Clin Orthop

The classification of Juvenile Chronic Arthritis. Clin Exp Rheum

Seronegative spondyloarthropathies : a review : part I: classification and differential diagnosis

https://www.um.edu.mt/library/oar/bitstream/handle/123456789/820/mmj050120.pdf?sequence=1&isAllowed=y

Seronegative spondyloarthropathies : a review : part I: classification and differential diagnosis

Abstract

Similar works

Full text

Available Versions

OAR@UM