AS classically progresses from sacroiliitis with in \202 amma- tory symptoms ascending the spine leading to spinal ankylosis, kyphosis/stoop and spinal restriction. Predicting class ical or less extensive disease is dif \201 cult in early AS. Osteoporosis, as shown by lum bar spine bone mineral density (BMD) measures might predict progres- sive disease. No known therapy halts or slows the natural history, although it is hoped anti-TNFA therapy may pro ve to have a disease-modifying role. AS can have a considerable socio-economic impact in so me, although not all patients. Key features on examination \200 Global restriction of lumbar spine movements in early AS and stiffening of the whole spine as AS progresses. Ultimately completely stiff spine with kyphosis. Reduced chest expansion compared to population reference for age/sex (at 4th intercostal space level). Peripheral j oint synovitis/arthritis is unusual with primary AS (apart from hip and shoulder joints). E nthesitis is variable and more prominent in lower limbs. (see Plate 4) Associated psoriasis may not be obvious. Any evidence of eye signs should prompt a ophthalmology referral to ru le out uveitis. Cardiovascular and respiratory examination is important with in established AS or those with symptoms. Associated conditions and co-morbidities \200 \200 AS is associated with iritis (40%). Cardiac conduction defects, aortic valve (AoV) incom- p etence and cardiomegaly occur. Anatomic evidence of AoV involvement can be seen in up to 20 % AS patients, but few have valvular dysfunction. About 50% patients with isolated AoV inco mpetence are HLA B27 +ve. Frank in \202 ammatory bowel disease or low-grade (often subclin ical) disease is commonly associated. Although rare, upper lobe lung \201 brosis can occu r and affected tissue be invaded by aspergillus. Deaths from all pulmonary causes are \201 ve times higher in AS compared with normal. This may relate partly to poor thoracic ex pansion and ventilatory dif \201 culty in the presence of lung infection and cardiac patho logy. Psoriasis and psoriaform skin lesions occur, arguably more commonly, in men compared with women. \200 Investigations Laboratory HLA B27 in >90% Caucasians; modest iESR or ESR normal (increases in ESR corresponds to severity of disease (e.g. i+ in AS patients with peripheral erosive a rthritis); normochromic normocytic anemia; IgAi. Radiographs In early AS, radiographs of SI Js and spine may be normal. As AS advances sacroiliitis may be become obvious and is usuall y bilateral. The sequence of sacroiliac changes over time typically consists of: \200 \200 Clinical features Key clinical features Delays in diagnosing AS are recognized. Taking a ca reful history and identifying that chronic in \202 ammatory-type back symptoms in someone <40 years may not re \202 ect a simple mechanical back disorder or a chronic pain syn- dro me, is probably the most important step in prompting appropriate imaging to be done to make a diagnosis. Initially, blurring of sub-chondral bone plate. Erosions (like postage stamp serrations) an d sclerosis of adjacent bone (typically iliac side \201 rst). Pseudo-widening of the SIJ. Gradual interosseous bridging and joint ossi \201 cation. Sclerosis persists or becomes m ore prominent. Bony ankylosis after a number of years. (see Plate 22) \200 \200 \200 Symptoms and signs \200 \200 \200 Key radiographic features in the axial skeleton Chronic in \202 ammatory spinal pain in a young adult. Fatigue. Low back pains radiating t o buttocks and posterior thighs. History of enthesitis (e.g. plantar fasciitis). Positive f amily history of SpA. Spinal movements are symmetrically restricted. Tenderness over enthes es (particularly pelvis/lower limb). Features on axial skeleton radiographs in AS patients \200 Early spinal features: vertebral squaring; small marginal syndesmophytes; erosion/sclerosis at verte- bral body corners [ \200\230shiny corner \200\231 sign/Romanus lesion (severe)]. Late spinal features: ankylosis of vertebral seg- ments (vertebral bodies or posterior seg ments; ossi- \201 cation of supraspinous and interspinous ligaments. Occurring at any tim e: discovertebral junction ero- sions or destruction; erosion/sclerosis of odontoid or cost overtebral joints; posterior spinal subligamen- tous erosion. Pelvis changes: sacroiliac pa thology (see text); iliac enthesophytes; ischial pole erosions/enthesophytes; symphysis pub is narrowing/sclerosis/erosion and ankylosis (late). \200 \200 \200 Key features in the history \200 In \202 ammatory spinal pains are invariable \200\223 pains are often associated with sti ffness, evolve insidiously, are promi- nent with immobility, are present on waking, can dis turb sleep, and ease with movement. Onset after the age of 45 years is very uncommon. Fatig ue, weight loss, and low-grade fever may occur and appear variable. Fatigue is often scored as the most troublesome symptoms by patients. \200 ANKYLOSING SPONDYLITIS 216 Typical radiographic features in the peripheral skeleton in established AS include: \200 DISH can be discriminated from AS (Table 7.2), but doing so using MR is not emphasized in t he literature. Osteitis Condensans Ilii can mimic sacroiliitis on pelvic radiographs. It us ually occurs in nulliparous women and is asymptomatic. Sclerosis occurs on the iliac side o f the lower SIJ, but the joint is normal. At the hip: in early disease \200\223 a distinctive enthesophyte on the lateral aspect of the femoral head. Eventually, a collar of these enthesophytes can form around the femoral h ead; diffuse concentric joint space narrowing; bony ankylosis (late). At the shoulder: conc entric joint space loss; superi- olateral humeral head erosions (if severe causing a \200 \230hatchet \200\231 appearance to the humeral head); erosive acromioclavicular joint (ACJ) and SCJ changes; CA liga- ment attachment bony proliferation/periosteal changes. Periphera l joints: periarticular osteoporosis less prominent than in RA; periarticular bone prolifer ation (fuzzy osteoperiostitis), e.g. at distal humeral epicondyles, patella margins, distal lateral femoral condyles; at attach- ments of carpal ligaments. At entheses: erosions, \202 uffy bone sclerosis and spurs. Changes often seen at plantar fascia origin, insertion of peroneal tendons in midfoot, Achilles \200\231 tendon or at lesser or greater trochanter s at proximal femur. Magnetic resonance imaging \200 Features of spondylodiscitis on T1- and T2-weighted MR are seen in AS though easy descrimin ation of AS/SpA- related spondylodiscitis compared with degeneration (Modic lesion) disciti s lesions has not been reported. The appearance of \200\230vertebral corner \200\231, \200\230oedema \200\231-type changes on both T1- and T2-weighted sequences is typical in AS . The cause of high signal in vertebral corners on T1-weighted lesions is unknown, but coul d be fatty change at sites of previous subenthesial osteitis. Spinal ligament enthesitis is probably poorly visualized on MR unless lesions are severe or numerous. Gd-enhancement app ears to add little overall in aiding a diagnosis of SpA or monitoring changes in in \202 a mmatory lesions after treatment. A number of robust MR scoring tools have been devised to m easure and monitor disease in AS. Consensus opinion suggests the 6-discovertebral unit (6-D VU) method devised under the auspices of SPARCC may be of most use. Figure 7.5 T2-weighted sagittal TSp in AS. High signal (in bone ?;osteitis) can be seen in 2 vertebal bodies in the TSp. Table 7.2 Discriminating AS from DISH DISH AS Usual age on onset >50y <40y TSp kyphosis Limitation of spinal mobility ++ ++ Pain d chest expansion Radiographs* ++ ++ Hyperostosis + + SIJ erosion** \200\223 ++ SIJ obliteration ++ Facet joint obliteration \200\223 Flowing ossi \201 cation ++ Ant. longitudinal ligament Syndesmophytes Florid non-marginal Usually marginal Enthesophytes Often extensive. Often erosions at base Usually no erosions Vertebral osteopaenia Bones often dense In early disease Figure 7.4 Coronal image fat-suppressed sequence MR. High signal (in \202 ammation) on bot h sides of the lower part of the SIJs. HLA B27 (Caucasians) 8% 95% HLA B27 (Afro-Caribbean) 2% 50% Differential diagnosis \200 Adapted from Calin (2004) and Resnick (2002). *Discriminating DISH from the spectrum of les ions that accompany axial musculoskeletal lesions in psoriatic spondylarthropathy is, by co mparison, less well emphasized in the literature. **Doubt whether SIJ changes may be due at ypical AS or DISH, may not be easily resolved by MRI alone. The presence of erosions on SIJ CT (in AS not DISH) may be better discriminatory investigation. In patients <15 years old: juvenile AS; juvenile psoriatic arthritis/spondylitis; enthesiti s-related arthropathy. In patients 15 \200\22350 years old: mechanical back pain; psoriatic spondylitis; reactive arthritis/spondylitis. In patients >50 years: as in those 15 \200 \22340 years old, but also diffuse idiopathic skeletal hyperostosis (DISH). CHAPTER 7 The spondylarthropathies 217 Management Objectives of disease management The main key objectives are symptom control, ma intaining functional ability and occupational potential, retaining spinal mobility, prevent ing osteoporosis, and monitoring for extra-musculoskeletal disease. A single RCT of le \202 unomide in AS concluded there was no bene \201 t over placebo. A Cochrane Review concluded there was inadequate evidence to support MTX use in AS. Anti-TNFA therapies have shown ef \201 cacy at an accepta- ble level of toxicity (Table 7.3). In \202 iximab treatment virtually clears spinal in \202 ammation evident by the appearance o f osteitis on spinal MR images; it also improves individual productivity lessening adverse physical and emotional factors and loss of work- days (sustained over 6 months). Etanercept therapy reduces spinal and SIJ in \202 ammation within 6 weeks of the start of therapy, s ustained over 24 weeks, as shown by MR. A Markov model of cost-utility over 5y suggests tha t the high cost of etanercept and in \202 iximab restricts ef \201 cient use in all patie nts with a BASDAI>4. Emerging data suggests adalimubab has similar ef \201 cacy to other a nti-TNFA inhibitors in AS. Physical therapies \200 Regular exercises are important in preventing or mini- mizing deformity. Spinal extension a nd deep breathing exercises should be done regularly. Formal physiotherapy is of value. Pos ture should be addressed. Group sessions including hydrotherapy may help. Regular swimming is considered the most appropriate aerobic exercise for AS patients. Control of pain/in \202 ammation \200 The responses to NSAIDs vary, but most patients require regular or \200\230as required \200\231 NSAIDs long-term. Phenylbutazone (butazoladin) is probably the most effective NSAI D for pain/stiffness in AS. Although the finding needs substantiating, regular NSAIDs may s low radiographic progression of AS. There is a signi \201 cant side-effect pro \201 le fr om long-term NSAID use. Other therapies Intravenous bisphosphonates may be helpful. Serial monthly pamidronate inje ctions improve symptoms (and BASDAI disease scores) in some patients. Surgery \200 Immunosupression \200 A number of spinal procedures may be useful. These include osteotomy, fusion of unstable se gments (caused by spondylodiscitis fracture), and laminectomies. For AS patients with ad vanced kyphosis/stoop, spinal osteotomy, generally improving sagittal spinal angle by a mea n 20 \200\22340 can be effective at improving functional ability, raising eyeline, and ma y have a role in reducing the risks from poor ventilatory capacity. There is some evidence for using sulphasalazine (SZP) in AS with peripheral arthritis thoug h its impact on the spine and peripheral enthesopathy is minimal. For AS patients with peri pheral arthritis unresponsive to NSAIDs and SZP, methotrexate (MTX) has been used and some bene \201 t reported. Table 7.3 A summary of randomized controlled trials of anti-TNFA therapies in AS 1e Outcome/response Medication/study Patients Design/duration Comments In \202 iximab* Small study. 3/35 in the in \202 iximab group had serious side effects 35 Randomized placebo- controlled for 12 weeks 18/35 (53%) in \202 iximab treated vs. 3/35(9%) placebo-treated had disease regression by 50% or more (BASDAI) Braun et al. (2002) 5 mg/kg iv at weeks 0, 2 and 6 Side effects frequent in both groups (82% vs. 72% placebo-treated) Randomized placebo controlled for 24 weeks ASAS20 achieved in 61% in \202 iximab treated patients vs. 19% placebo treated (p < 0.001) 357 screened; 201 in \202 iximab treated and 78 placebo van der Heijde et al. (2005) 5 mg/kg iv at weeks 0, 2, 6, 12, 18 Etanercept** All ASAS components improved. A later study showed sustained improvement in patients over 2 years 277 Randomized placebo- controlled for 24 weeks ASAS20 achieved in 57% of 138 etanercept vs. 22% of 139 placebo treated pts (p < 0.001) 25 mg sc \2272/week** Davis et al. (2003) Davis et al. (2005) Calin et al. (2004) 84 Double blind placebo- controlled for 12 weeks ASAS20 in 26 (60%) etanercept vs. 9 (23%) pts; p < 0.001; CI 17 \200\22356% Adalimumab ASAS20 in 58% adalimumab vs. 21% placebo pts (p < 0.001) ASAS40 at 12 and 24 weeks by some patients 315 Double blind placebo- controlled/randomized 2:1 adalimumab:placebo/ 12 weeks 40 mg sc fortnightly van der Heijde et al. (2006) Have been shown in separate studies to reduce attacks of uveitis in AS patients. **In a lat er study, 50 mg weekly was shown to be as effective as 25 mg twice weekly. ANKYLOSING SPONDYLITIS 218 \200 Resources Assessment tools Self-assessment tools: BASDAI, BASFI, and other assess- ment too ls (e.g. ASQoL, Dougados Functional Index, BASMI, etc) can be downloaded in a number of lan guages from the ASAS Workshop page link at the ASIF website (www.asif.rheumanet.org). A ref erence list of original publications detailing assess- ments can be reviewed at www.rheumat ology.org/ publications/abbreviations/index.asp Key points of spinal osteotomy are shown below. Osteoporotic fractures in the AS spine can be severe and dif \201 cult to \201 x. Surgery is always challenging. Intervention crite ria/thresholds employed to guide pre- ventive therapy for osteoporotic fractures in AS have not been derived. Spinal osteotomy in AS: key points \200 Surgery and anesthesia is relatively high risk and challenging. Neurological morbidity can be severe/ permanent. Surgery should only be undertaken in specialized centers by experienc ed staff. Technically, osteotomies of lumbar, thoracic or cervical spine vertebrae can, in theory, be considered. There are 3 main (posterior approach) techniques (reviewed in Van Ro yen & De Gast, 1999): opening, closing, or polysegmental wedge osteotomies. Closing wedge o steotomy procedures are associated with the lowest incidence of complications. The theoreti cal bene \201 ts of improving functional ability, reducing conventional AS-related pulmona ry mor- bidity, general well-being and spinal symptoms in the long-term has not been establ ished in (the almost exclsively retrospective) series of patients reported. Guidelines ASAS guidelines derived by physician consensus based on a Delphi study undertake n by the group. See www. asas-group.org/ NIHCE Guidelines (www.nice.org.uk/) cover the use of anti-TNFA therapies for NHS patients in the UK. These were derived by (chie \202 y) hea lth economists/clinicians appointed by the UK Government who were cognate of the BSR guidel ines. Patient organizations/information AS self-help organizations of various countries are liste d on the ASIF website (www.asif.rheumanet.org). Informing licensing authorities about dif \201 cult driving may vary between countries. In the UK, where there is signi \201 - cant neck restriction, there is a requirement to inform the DVLA. Useful information regarding i ssues of the patient \200\231s point of view is summarized in Rogers 2003. Webpage on Spond ylarthritis. See ACR website www. rheumatology.org/public/factsheets/ Prognosis Poor prognostic indicators in early disease \200 \200 \200 \200 Polyarticular synovitis. High acute phase response. Hip involvement. Osteoporosis (lumbar v ertebrae). References Benjamin M, McGonagle D, Davis JC, van der Heijde DM, Braun J, et al. Sustained durability and tolerability of etanercept in AS for 96 weeks. Ann Rheum Dis 2005; 64: 1557 \200\22362. Likely poor prognostic indicators in established disease \200 \200 \200 \200 \200 \200 Complete thoracic spine ankylosis. Cardiovascular and respiratory disease complications. Ex cessive continual NSAID use. Spinal fracture. Continued high acute phase response/anemia. P olyarticular synovitis. Boonen A, et al Employment, disability and work days lost in patients with AS \200\223 a cross-sectional study of Dutch patients. Ann Rheum Dis 2001; 60: 353 \200\2238. Boulos P, Dougados M, Macleod SM, Hunsche E. Pharmacological treatment of AS: a systematic review. Drugs 2005; 65: 2111 \200\22327. Bowness P. HLA B27 in health and disease: a double edged sword? Current controversies Diagnostic issues \200 \200 Rheumatology 2002; 41: 857 \200\22368. Braun J, Brandt J, Listing J, et al. Treatment of active AS with in \202 ixi- mab: a rando mized controlled multicentre trial. Lancet 2002; 359(9313): 1187 \200\22393. How HLA B27 predisposes to disease. How autoimmune processes speci \201 cally lead to path ology at entheses and sub-enthesial bone marrow. How best to invoke strategies that reduce the delay in diagnosing AS (e.g. triage of chronic back pain patients). How best to image S IJs and spine in early AS to make a \201 rm diagnosis (MR of SIJs may be more sensitive i n detecting sacroiliitis but classi \201 cation criteria depend on radiographic changes be ing present). Braun J, Pham T, Sieper J, et al. International ASAS consensus state- ment for the use of a nti-TNF agents in patients with AS. Ann Rheum Dis 2003; 62: 817 \200\22324. Calin A. Ankylosing spondylitis. In: Isenberg DA, Maddison PJ, Woo P, Glass D, Breedveld FC (eds) Oxford Textbook of Rheumatology, 3rd edn. Oxford: Oxford University Press, 1994: 754 \200\22366. Calin A, Dijkmans BA, Emery P, et al. Outcomes of a multicentre randomized clinical trial o f etanercept to treat AS. Ann Rheum Dis 2004; 63: 1594 \200\2236000. Management/treatment issues \200 \200 Chen J, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Do NSAIDs slow AS progression (disease-modifying)? What role do potent iv bisphosphonates h ave in controlling pain/in \202 ammation or modifying disease? Do oral bisphosphonates hav e a relevant symptom modifying or disease-progression slowing role? Do bisphosphonates redu ce fractures in AS? Are anti-TNFA medications safe in the long-term? Do they modify disease progression and if so are they equally effective on axial and peripheral disease Cochrane Database Syst Rev 2004; 3: CD004524. Davis JC Jr, van der Heijde D, Braun J, et al. Recombinant human tumor necrosis factor rece ptor for treating AS: a randomized controlled trial. Arthritis Rheum 2003; 48: 3230 \200 \2236. Francois RJ, Neure L, Sieper J, Braun J. Immunohistological examina- tion of open sacroilia c biopsies of patients with AS: detection of TNFA in 2 patients with early disease and TGFB in 3 more advanced cases. Ann Rheum Dis 2006; 65: 713 \200\22320. \200 Keat A, Barkham N, Bhalla A, et al. BSR Guidelines for prescribing TNF-alpha blockers in ad ults with AS. Report of a working party of the BSR. Rheumatology 2005; 44: 939 \200\22347. CHAPTER 7 The spondylarthropathies 219 Van der Heijde D, Kivitz A, Schiff MH, et al. Ef \201 cacy and safety of adalimumab in pat ients with AS: results of a multicenter, rand- omized, double blind, placebo-controlled tri al. Arthritis Rheum 2006; 54: 2136 \200\22346. Kollnberger S, Bird L, Sun M-Y, et al. Cell surface expression and immune receptor rocognit ion of HLA B27 homdimers. Arthritis Rheum 2002; 46: 2972 \200\22382. Maksymowych WP, Inman RD, Salonen D, et al. Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index for Assessment of Spinal Inflammation in Ankylosing Spond ylitis. Arthritis Rheum 2005; 53: 502 \200\2239. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing s pondylitis: a proposal for modi \201 cation of the New York criteria. Arthritis Rheum 1984 ; 27: 361 \200\2238. Van Royen BJ, DeGast A. Lumbar osteotomy for correction of thoracolumbar kyphotic deformity in AS. A structured review of 3 months of treatment. Ann Rheum Dis 1999; 58: 399 \200\2234 06. Resnick DD. Diffuse idiopathic skeletal hyperostosis. In: Resnick DD (ed.) Diagnosis of Bon e and Joint Disorders, 4th edn. Philadelphia: WB Saunders, 2002, 1476 \200\223500. Wanders A, Heijds D, Landewe R, et al. NSAIDs reduce radio- graphic progression in patients with AS: a randomized clinical trial. Arthritis Rheum 2005; 52: 1756 \200\22365. Resnick DD. Ankylosing spondylitis. In: Resnick DD (ed.) Diagnosis of Bone and Joint Disord ers, 4th edn. Philadelphia: WB Saunders, 2002, 1023 \200\22381. Rogers FJ. Ankylosing spondylitis \200\223 the patient \200\231s point of view. In: Calin A and Taurog JD(eds) The Spondylarthritides. Oxford: Oxford University Press, pp. 251 \200 \22365. Van der Heijde D, Dijkmans B, Geusens P, et al. Ef \201 cacy and safety of infliximab in p atients with AS: results of a randomized placebo-controlled trial (ASSERT). Arthritis Rheum 2005; 52: 582 \200\22391. PSORIATIC ARTHRITIS 220 Psoriatic arthritis De \201 nition PsA is a chronic autoimmune in \202 ammatory arthropathy. In adults, there is no single agreed satisfactory de \201 nition en- compassing all forms of PsA. Classi \201 cation of PsA pro- posed 35 years ago listed the necessary presence of 3 features: in \202 ammatory arthritis, psoriasis and negative rheumatoid factor (Moll & Wright, 1973). I n 1984 new cri- teria expanded the set of potential features classi \201 able under a diag nosis of PsA, but essentially required the pres- ence of psoriatic skin or nail disease wit h either a periph- eral or axial pattern of disease. The component features of de \201 nin g \200\230peripheral \200\231 and \200\230axial \200\231 were both restrictive and imprec ise, and the criteria were not very user friendly. Cri- teria did recognize for the \201 rst time though the presence of juxta-articular new bone as important. Epidemiology \200 Psoriasis (Ps) affects 3% of the population (North Europe). Studies suggest prevalence of P sA in Ps patients is about 40% and in the population up to 1%. Estimates suggest that about 20% of patients develop PsA before Ps, in some cases by many years. Old epide- miology dat a might underestimate PsA prevalence. The new CASPAR criteria, applied in appropriate studi es in Primary Care should help clarify the situation. There is probably equal sex prevalenc e with peak presentation between 35 \200\22355 years old. Etiology and pathophysiology Genetic \200 Subsets of disease were increasingly recognized, although entheseal-predominant disease is a relatively recent determined subgroup. Polygenic (familial aggregation); high MZ twin concord- ance; HLA associations found with B 13, B16 (B38 and B39), B7, B17, B27, Cw6, DR4, and DR7. Susceptibility to PsA may also resi de at chromosome 16q, a region overlapping with CARD15, a susceptibility locus for Crohn \200\231s disease. There are 3 main mutations. The peptide, located in monocyte, macrophage , and dendritic cell cytoplasm, recognizes certain bacterial components though how immunopa thology subse- quently develops is uncertain. The clinical spectrum of PsA \200 \200 \200 \200 \200 \200 Predominantly DIP Joint involvement Arthritis mutilans (digit \200\230telescoping \200\231 ) Symmetrical polyarthritis Asymmetrical oligoarthritis Spondylitis predominant Entheseal p redominant Environment PsA and Ps is triggered, and exacerbated by B-haemolytic streptococci and HIV. Trauma and stress have also been identi \201 ed as potentiating factors. However, subgroups are unstable over time and with treatment, and their de \201 nition is dependent on method of detection. The classi \201 cation of the PsA (CASPAR) study group c riteria have been based on observations of 1000 PsA and control patient data, and have high sensitivity (0.91) and specificity (0.99). Criteria were compared against a gold standard of clinician opinion (Table 7.4). Immunopathology \200 Information is incomplete. Studies have relied on obtaining material from blood and synoviu m of affected patients, and relatively little is known about the pathophysiology in enthesi al, periosteum, and other bone sites \200\223 sites of frequent involvement in PsA. In syn ovium (as in the skin in Ps) there are dilated capillaries and monocyte-rich perivascular i n \201 ltrates. Th1 cytokines, such as Il-2 and IFNG are i in skin, but not in synovium; P aired skin and synovial samples show different oligoclonal patterns of TcR usage and T-cell s from psoriatic skin transferred into SCID mice can induce psoriasis, but not arthritis. T hus, T-cell recognition patterns may differ in the two tissues and skin, and joint disease might be mediated by different cells. Increased TNFA has been detected in skin and joint \202 uid of patients with PsA. Table 7.4 CASPAR classi \201 cation criteria for PsA. In \202 ammatory articular disease (joint, spine or entheseal) with 3 or more points from the following Current psoriasis (2 pts) Skin or scalp disease judged by a rheumatologist History of psoriasis From patient, dermatologist, rheumatologist, or GP Family history of psoriasis In \201 rst or second degree relative Psoriatic nail dystrophy Onycholysis, pitting or hyperkeratosis Negative rheumatoid factor By any method except latex Current dactylitis Entire digital swelling Prognosis and natural history \200 History of dactylitis Recorded by rheumatologist Undoubtedly PsA can be mild and have little impact on functional abilities, even in the lon g-term; however, pro- gressive PsA impacts substantially on employment social and \201 na ncial stability and healthcare use/costs. Oligoarticular joint disease is associated with a relatively benign prognosis. Erosive, deforming arthritis occurs in about 40 \200\22360% o f PsA patients attending rheumatology clinics. Adverse prognostic factors appear to be poly arthritis, greater HAQ, and increase use of DMARDs. Radiological evidence of juxta- articular new bone On hand or foot excluding osteophytes See Taylor W et al., 2006 The de \201 nition of in \202 ammatory joint, spine, or entheseal disease may require som e pause for thought and possibly further study. Conventional de \201 nitions (e.g. feature s of synovitis in RA or IBP in AS may not be appropriately trans- ferred given the differen ce in type of causative lesions. CHAPTER 7 The spondylarthropathies 221 Clinical features Key clinical features \200 \200 \200 \200 \200 \200 \200 Common signs of the pelvis include hip joint restriction, tenderness of symphysis pubis (os teitis pubis), sacroiliitis indicated by positive sacroiliac stress tests, and tender- ness over entheses particularly greater trochanters, ASISs, and PSISs. In \202 ammatory joint and/or spinal pains. Asymmetric or unilateral symptoms/lesions. His tory of psoriasis or family history of it. History of other SpA (or SpA-linked) condition. Dactylitis of toes or \201 ngers. Enthesitis. Ps or psoriaform rash (at any time) Co-morbidities PsA is linked to other SpA conditions and SpA-related lesions, such in \202 ammatory bowel lesions (16% in one study) and acute anterior uveitis (<10%). \200 \200 Gouty arthritis may occur in 5 \200\2237% PsA patients. Ps and psoriasis can occur de novo or be exaceberbated, in HIV+ people Studies that have linked Ps and PsA to coeliac disease have done so on the basis of suboptimal serological testing, although ultimately detailed a nd appropriate clinco- imaging appraisal of appropriate patient groups has not been done. S APHO syndrome has been proposed by some as a clinical syndrome contiguous with the spectrum of PsA. Key features in history \200 PsA can present with Ps, long after Ps started or before it, sometimes years before. A fami ly history of Ps is not unusual. Ps can be mild and ignored by the patient. Direct and repe ated questioning about rashes in typical sites for Ps is often helpful (e.g. in ears, umbil icus, posterior hairline, natal cleft, around waist). A history detailing all previous musc uloskeletal problems, even if seemingly trivial to the patient, may be informative (e.g. pr evious recurrent heel, groin, pelvic or elbow pains, in \202 ammatory-type back pains, etc ). Establishing whether there is or has been in \202 ammatory back or neck pain may be rel evant. PsA lesions may have been triggered by trauma. Be aware of \200\230injuries \200 \231 that don \200\231t settle satisfactorily. Groin and anteromedial thigh pain may be fro m hip joints, symphysis pubis, or adductor tendons. Previous plantar fasciitis and \200 \230tennis elbow \200\231 may be relevant to making a diagnosis of chronic PsA. \200 Investigations Laboratory \200 \200 ESR and CRP can be normal or only modestly raised. Rheumatoid factors (RFs) and anti-CCP an tibodies have been described in PsA, but their presence requires very careful scrutiny of d iagnosis. Imaging Radiographs Careful evaluation of current and previous radiographs can be enlighten ing in highlighting bony changes. \200 \200 Key features on examination Upper limbs \200 In early PsA radiographic features may be absent. In established PsA, radiographic abnormal ities may exist where symptoms are minimal or not evident. There \200\231s a range of radio graphic signs in PsA, often mistaken for degenerative disease. Axial PsA may be disclosed b y radiographs. Without a high index of suspicion, appearances, particularly in the neck, ma y be confused with degenerative changes. Asymmetric appearance to small hand joint and \201 nger swelling \200\223 may be dactyli tis, which is often associated with underlying MCPJ or PIPJ erosions. DIPJ changes in advan ced PsA can look just like OA, although PsA associated with nail pits and onycholysis. Ofte n tender without much swelling at wrists. Thumb CMC area is often affected. Enthesitis of l ateral humeral epicondyles is common. Other entheses to check for tenderness: deltoid origi n, medial humeral epicondyle. \200 \200 \200 Ultrasound (US) \200 There is increasing experience using US to identify dactylitis and enthesitis. Discriminati ng patterns of soft-tissue abnormality around joints and tendons in RA and PsA may be an ac hievable, and extremely worthwhile, goal using US. Pelvis and lower limbs \200 In some PsA types synovitis may not obviously accompany pain in the knees, but there may be peri-articular tender- ness at entheses (e.g. inferior patella pole and patella ligament i nsertion). Synovial thickening and effusions at the knees can be, but are not always, massi ve. Synovitis and bony tenderness around the hindfoot is common. Tenderness over medial cal caneal tubercle denotes enthesial involvement of plantar fascia origin. Midfoot restriction of movement is common. Hallux limitus (early) and rigidus (late) can reflect chronic osteo -periostitis of the great toe \200\223 a common \201 nding in PsA: indolent dactylitis m ay be present. Nail changes may look non-specific, but extensive subungual hyperkeratosis i s typical of Ps-related disease. Typical features on radiographs in patients with PsA \200 General: enthesophytes; periosteal new bone (often juxta-articular); often no periarticular osteopaenia. Pelvis: irregular/unilateral sacroiliac changes; hip arthritis; enthesophytes ; osteitis pubis. Spine: syndesmophytes; facet joint arthritis; poste- rior element new bon e formation (enthesophytes and periosteal apposition); spondylodiscitis. Peripheries: DIPJs : juxta-articular bone; widening joint space; \200\230 \202 ange \200\231 osteophytes. Ph alanges: dactylitis; diaphyseal thickening; tuft changes; soft tissue swelling (dactylitis) \200 Axial skeleton \200 Signs in the neck and spine are non-speci \201 c, although marked global restriction of mo vement can occur. PSORIATIC ARTHRITIS 222 Figure 7.6 DIPJ arthritis in PsA. Flanging of periarticular bone, increased joint width (ri ght), abnormal distal phalanx bone texture changes (in the digit on right with dactylitis) and a paucity of OA features (e.g. subchondral sclerosis, cysts and osteophytes). Figure 7.8 Juxta-articular new bone (periosteal whiskering) of the great toe distal phalanx in PsA. Note the relatively normal joint appearance. Figure 7.9 Juxta-articular bone at calcaneocuboid joint. A plantar spur can be associated w ith PsA. MR-identi \201 ed changes in the nail-bed associated with DIPJ arthritis may be speci \201 c for PsA and may be detect- able using extremity (0.2T) MR. Differential diagnosis \200 Figure 7.7 PsA neck. Marginal and paramarginal syndesmophytes, \202 orid posterior elemen t periosteal apposition and facet joint involvement. Where there is obvious chronic synovitis in a number of small joints the main differential diagnosis is RA. Generalized OA will be the main differential diagnosis of multiple DIPJ in volvement. Look for nail pits (associated with PsA not OA). Be suspicious of a diagnosis of OA in a patient with Ps (or previous history of it or Ps in \201 rst degree relative) in an \200\230unusual \200\231 joint for OA (e.g. ankle or subtalar), where there has been n o previous signi \201 cant trauma. Like PsA, all SpAs are characterized by dactylitis, joi nt and enthesis lesions. The enthesopathic/periosteal lesions of PsA can be mistaken for \201 bromyalgia. MR Distinctive patterns of MR abnormality for dactylitis and PsA-related DIPJ arthritis are now recognized, although results need substantiating: \200 MR has not yet been shown to discriminate sarcoid from PsA/SpA-related dactylitis. MR may n ot be as useful in identifying in \202 ammatory spinal lesions in PsA as it is in AS. CHAPTER 7 The spondylarthropathies 223 Patients treated with MTX are 9 times more likely to bene \201 t and 5 times less likely t o stop treatment com- pared with patients treated with gold compounds \200\223 the latter having shown some ef \201 cacy in PsA, given either as aurano \201 n 3 g/day or monthly i njections. RCT data have shown sulphasalazine, le \202 unomide, and anti-TNFA therapies ca n improve PsA symptoms in the short term. Le \202 unomide and notably anti-TNFA therapies have a signi \201 cantly improve Ps as well. Ciclosporin A, antimalarials D-penicillamine and azathio- prine show some ef \201 cacy in small, open label studies. Antimalarials can aggravate Ps, however. Overall, conventional DMARDs have not shown ef \201 cacy in treatin g axial PsA disease. Prognosis \200 Worse prognosis is associated with polyarticular presen- tation, high ESR/CRP and IgA and H IV status. Persistent dactylitis is associated with erosive disease of underlying small joi nts. HLA B27, B39 and DQw3 are associated with disease progression but DR7 is protective. S tudies linking synovial \202 uid constituents to prognosis fail to represent the complete range of PsA subtypes. Figure 7.10 PsA toe. Juxta-articular new bone (periosteal apposition) of distal \201 rst metatarsal head. Current controversies Diagnostic issues \200 Chronic sarcoid, like PsA, can involve entheses and periostea particularly around the hindf oot and lower leg (e.g. plantar fasciitis). PsA spondylitis can be mistaken for chronic mec hanical back (or neck) pain. Most controversies probably arise as a consequence of varied case ascertainment in clinical studies. Is PsA one condition with many and varied musculoskel- etal lesions or are there distinct conditions? Can PsA be adequately defined without extensive Primary Care based cap ture of a broad range of possibly affected patients with and without Ps? Will CASPAR perfor m appropriately in this respect? What is the main lesion in PsA? Enthesitis? Periostitis? S ynovitis? A review of the foremost textbook of muscu- loskeletal radiology would suggest no n-articular bone- related lesions are the most frequent across the PsA disease spectrum (se e Resnick 2002). What is the prevalence of PsA-sine-Ps? Is dactylitis always clinically evi dent? What is the spectrum of PsA-related spinal disease? For example how commonly is spond ylodiscitis or facet joint arthritis a feature of Psoriatic spondylitis? Do current diagnos tic methods under-estimate Ps-related musculoskeletal disease? In the spine? Current method s of identifying Psoriatic Enthesopathy are suboptimal and there may be diagnostic confusio n in patients otherwise thought to have \201 bromyalgia. Does MR discriminate PsA from al l phases of OA in DIPJs particularly in early disease? Treatment Objectives of disease management \200 To control symptoms and prevent disability through judicious use of NSAIDs and immunosuppre ssants. One-fourth of patients with PsA are dissatis \201 ed with the treatment they recei ve (see NPF 2002). Although PsA is often judged to be indolent, evidence suggests that, lif elong, PsA is associated with signi \201 cant indices of disability. \200 \200 Physical therapies There is little evidence to suggest what role physical therapy plays in PsA. Hand therapy review for assessing functional impact, and utilizing splinting and joint protection methods. Control of pain NSAIDs probably have a variable effect. Trying full dose over 4 weeks and s wapping to an alternative if no satisfactory effect occurs is appropriate. Immunosupression There is a de \201 cit of therapeutic trials in PsA. This and other subop timal aspects of the care of PsA patients have been addressed in principle through the aims of GRAPPA, an international group of clinicians convened to work toward facilitating resea rch into PsA. \200 Management issues \200 The role of physiotherapy and whether exercise helps or worsens PsA-related spondylitis in the short-term (symptom modi \201 cation) and long-term (?accelerated spinal damage). What measures should be adopted to gauge results in therpaeutic studies? Should different datas ets be used for different disease subtypes? Are anti-TNFA therapies cost-effective in PsA i n the long-term? Do they prevent radiological progression? Historically the use of therapies in PsA has followed from their established use in patient s with RA. Though anecdotal evidence for its ef \201 cacy can be found, methotrexate (MTX) has not been extensively studied. Studies suffer from low patient numbers, too short follo w-up, and other methodological \202 aws. PSORIATIC ARTHRITIS 224 Table 7.5 A summary of the major randomized controlled therapeutic trials in PsA Drug (reference) Patient characteristics RDBPCT* details Statistically signi \201 cant results Sulphasalazine (SZP) Clegg et al. (1996) 221 patients 36-week study. SZP 2 g/day. SZP signi \201 cantly effective according to composite pre-de \201 ned response measure. High response rate in placebo arm (44%) 24-week study. LEF 100 mg/day for 3 days then 20 mg/day 59% LEF vs. 30% placebo responded judged by PsARC Le \202 unomide (LEF) Kaltwasser et al 2004