features Clinical features 1. In \202 ammatory back pain 2. Arthritis 3. Enthesitis 4. Dactylitis \200\224sausage-like \201 ngers 5. Uveitis 6. Psoriasis 7. Crohn \200\231s disease/ ulcerative colitis 8. Good response to NSAIDs 9. Family history of spondyloarthritis 10. HLA-B27-positive 11. Elevated C-reactive protein Radiological features of sacroiliitis: 1. MRI features of sacroiliitis (i.e., bone marrow edema) 2. Radiographic sacroiliitis The ASAS classi \201 cation criteria have a sensitivity of 82.9%, and a speci \201 city o f 84.4% Rudwaleit M, et al. Ann rheum Dis 2009; 68: 777 \200\223783. CHAPTER 8 The spondyloarthridities 288 Table 8.2 Assessment of Spondyloarthritis International Society (ASAS) classi \201 cation criteria for peripheral spondyloarthritis Classi \201 cation requires the following: 1 clinical feature + 1 associated feature, OR 2 clinical features In either case, at least one clinical feature must be arthritis, ethesitis, or dactylitis. Clinical features 1. Arthritis (typically asymmetric, affecting predominantly the lower extremities) 2. Enthesitis 3. Dactylitis 4. In \202 ammatory back pain 5. Family history of spondyloarthritis Associated features: 1. Uveitis 2. HLA-B27 2. Preceeding genitourinary or gastrointestinal infection 3. Psoriasis 4. In \202 ammatory bowedl disease 5. Sacroiliitis on imaging The ASAS classi \201 cation criteria have a sensitivity of 77.8%, and a speci \201 city o f 82.8% for peripheral spondyloarthritis Rudwaleit M, Curr Opin Rheumatol 2010; 22: 375 \200\22380. DIAGNOSTIC CRITERIA AND CLINICAL SUBSETS 289 Table 8.3 Comparison of the seronegative spondyloarthridities Feature AS REA PA EA More 4 20 \200\22330 4 = 5 Any age 4 = 5 Any age 4 = 5 Any age Sex Age onset (years) Onset Gradual Sudden Variable Gradual % HLA B27 positive 95 20 (50 if sacroiliac disease is present) Sacroiliitis Always Often Often Often Peripheral joint disease Lower limb > upper Usually lower limb Usually lower limb Usually lower limb Enthesitis Present Present Present Present Uveitis Common Not common Not common Not common Conjunctivitis Not seen Not common Not seen Not seen Urethritis Not seen Rare Not seen Not seen Skin disease Not seen Rare Very common Rare Mucosal disease Not seen Not seen Not seen Not common AS, ankylosing spondylitis; REA, reactive arthritis; PA, psoriatic arthritis; EA, enteropat hic arthropathy. CHAPTER 8 The spondyloarthridities 290 Ankylosing spondylitis Epidemiology \200 Few clinicians rely solely on the criteria; most would consider the diagnosis of ankylosing spondylitis (AS) in any case of symptomatic in \202 ammatory back pain with radiographic evidence of sacroiliitis. The modi \201 ed New York criteria for AS, shown in Table 8.4, are better at capturing well-established disease; many patients with early AS would not meet the radio logic criteria, which requires unequivocal evidence of sacroiliitis on a plain radiograph. The dif \201 culty comes in recognizing early disease or subtle radiological change. There is often an insidious onset of back pain and morning stiffness that tends to improve with exercise. MRI is more sensitive than plain radiographs for detecting sacroiliiits, but occa sionally, sacroiliitis is a chance \201 nding in the absence of pain. Patients are typically <40 years of age with a male to female ratio of approximately 3:1. The condition occurs more frequently in Caucasian populations. In American Indians, where HLA B27 prevalence is high, AS is particularly frequent, whereas th e condition is less common in African-Americans, and rarer still in Sub-Saharan Africans, r e \202 ecting the declining prevalence of HLA B27 in these groups. Prevalence estimates in Caucasians range from 0.05 \200\2230.23% in adults. This may be an underestimate as people with mild symptoms may not seek medical advice. As previously stated, HLA B27 typing has led to greater understanding of the spondyloarthropathies, but should not be considered a diagnostic test or necessary f or the diagnosis of AS. Up to 5% of Caucasian patients with AS are negative for HLA B27. Clinical features of AS \200 The principal feature of the condition and allied diseases i s enthesitis , i.e., \201 brosis and ossi \201 cation of ligament, tendon, and capsule insertions into bone (the entheses), mainly in the region of the disks and sacroiliac joints. Synovitis also occurs, typically in the larger peripheral joints (hips and knees in particu lar). 20 \200\22340% of patients have some degree of peripheral joint disease at some stage during their illness, moreso in women than in men. Approximately 50% of patients with adul t AS will develop hip arthritis and some of these will need surgery. The standardized mortality ratio is 1.5; this increased mortality is due to cardiac valve a nd respiratory disease, amyloidosis, and fractures. \200 Like other forms of chronic dise ase, AS patients have a signi \201 cant risk of having to alter or give up work. Although recognized as typical of as, few patients progress to the classical late \200\234 bamboo spine. \200\235 When the spine does fuse (with \200\234syndesmophytes \200\235 brid ging the gap between vertebral bodies) microfractures can occur leading to acute episodes o f severe pain and ANKYLOSING SPONDYLITIS 291 Table 8.4 Diagnostic criteria: Modi \201 ed New York Criteria Clinical criteria: Low back pain and stiffness for >3 months improving with exercise but no t relieved by rest Limitation of lumbar spine movements in sagittal and frontal planes Limi tation of chest expansion relative to normal values for age and sex Radiological criteria: Greater than or equal to Grade II bilateral sacroiliitis Grade III or IV unilateral sacroiliitis Combined diagnostic criteria: De \201 nite AS if 1 radiological and 1 clinical criterion Probable AS if 3 clinical criteria or a radiological criterion without signs or symptoms sa tisfying the clinical criteria Van der Linden et al. Evaluation of diagnostic criteria for ankylosing spondylitis: a propo sal for modi \201 cation of the New York Criteria. Arthritis Rheum, 1984; 27: 361 \200\223 8. spondylodiscitis, a term given to collapse of the vertebral end-plate and destruction of th e disc \200\223bone border. This process is usually self-limiting, requiring rest and analgesia for up to 3 weeks. Most spinal disease is limited to chronic low-grade pain and stiffness with clinical evidence o f a symmetrical reduction in spinal mobility. Patients may have insertional tendonitis at several other common sites including the Achill es tendon, intercostal muscles, plantar fascia, and dactylitis of the hands and feet. Extra-articular disease in AS \200 Constitutional features of fatigue, weight loss, low-g rade fever, and anemia are common. Fatigue as opposed to pain or stiffness can be the most troublesome symp tom for many patients. Iritis occurs in up to 40% of cases but has little correlation with disease activity in the spine. There are no known triggers for this condition and although self-limiting, topical or systemic steroids may be required in severe cases. Iritis is usually unilateral. Upper lobe, bilateral pulmonary \201 brosis is a recognized feature of the disease. Occas ionally the \201 brotic area is invaded by aspergillus with changes mimicking tuberculosi s. Treatment of the \201 brosis is of not effective. Pleuritis can occur as a consequence of insertional tendonitis of the costosternal and costovertebral muscles. Fusion of the th oracic wall leads to rigidity and reduction in chest expansion. Ventilation is maintained b y the diaphragm; however, there is a threefold increased risk of death from a respiratory c ause compared with a normal population. CHAPTER 8 The spondyloarthridities 292 Cardiac involvement includes aortic incompetence, cardiomegaly, and conduction defects. Of the 20% of patients with aortic valve disease, the majority are clinically undetectable. Neurological complaints are not a feature of AS, although nerve root entrapment or spinal c ord/cauda equine compression can occur as a result of spinal fusion or fractures. Primary renal involvement is uncommon and if present may be due to coexistent medical conditions, NSAID use, or renal amyloidosis. \200 Osteoporosis is an u nder-recognized \201 nding. Estimates of prevalence range from 20 \200\22360%, increasing with age and disease duration, and disease is largely con \201 ned to the axial skeleton. Bone density scanning may be inaccurate in the lumbar spine due to the presence of syndesmophytes late in the disease. Studies suggest that bone loss occurs early and during the acute in \202 ammatory stage of the disease and that fur ther bone loss, long-term, is rarely seen. Micro-fractures may occur with trauma but the cl assical vertebral compression and wedge fractures of osteoporosis are rarely seen. Further work needs to be done to establish the need for, and ef \201 cacy of, current osteoporosis therapies for patients with AS. Diagnostic evaluation of AS \200 There is little correlation between any of the in \202 ammatory markers and disease activity or clinical symptoms. Radiological evaluation is the most helpful form of investigation. Plain anteroposterior view radiographs are of the most value, but may not show early change s. A false positive result is common due to projection artifacts. Early changes include los s of the subchondral sclerotic line. Changes may initially be asymmetric. Later \201 ndin gs include the more classical \201 ndings of subchondral sclerosis, erosions, and \201 nally ankylosis. Radionuclide scanning may be sensitive but is non-speci \201 c and may be more confusing than helpful. CT provides excellent views of the SI joints (in exchange for a higher radiation dose). MRI may demonstrate joint erosions, and also bone edema and fatt y change in marrow that are not detected by CT or plain radiographs. The main radiological features of \200\230primary \200\231 AS and that associated with in \202 ammatory bowel disease are: \200 symmetrical sacroiliac changes \200 ascending spread of disease \200 facet joint involvement \200 squaring of vertebrae \200 synde smophytes \200 ossi \201 cation \200 osteitis pubis. It is said that AS associated reactive arthritis or psoriatic arthropathy (PsA), i.e., seco ndary AS, tends to differ by being far less severe radiologically, with often asymmetrical sacroiliac disease and random spinal involvement. It is important to differentiate syndesmophytes from osteophytes. Syndesmophytes are vertical; osteophytes are horizontal, and occur in association with disc -space narrowing. ANKYLOSING SPONDYLITIS 293 AS should be distinguished from diffuse idiopathic skeletal hyperostosis (DISH). The two conditions are compared in Table 8.5. Disease status and prognostic indicators in AS \200 There are validated self-administered instruments de \201 ning disease status in AS. Since one lacks the advantage of valuable laboratory tests, it is helpful tha t there is a good correlation between the self-reporting of symptoms and observed clinical status of patients with AS. Instruments for assessing disease status include indexes produced by the Royal National Hospital for Rheumatic Diseases, Bath, UK, namely the Bath Ankylosing Sp ondylitis Functional Index (BASFI), Disease Activity Index (BASDAI) (see Table 8.6), Metrol ogy Index (BASMI), and Radiology Index (BASRI). It is dif \201 cult to de \201 ne outcome for individual patients when considering prognosis. The main predictive factors in AS appear to be: \200 early hip involvement \200 an ESR > 30 \200 poor initial response to NSAIDs \200 early loss of lumbar spine mobility \200 presence of dactylitis \200 oligoarticular disease \200 onset < 16 year s \200 low social \200\223educational background \200 sporadic disease rather than fami lial. Table 8.5 Differentiating diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing sp ondylitis (AS) Feature DISH AS Age of onset (years) Usually > 50 Usually < 40 Kyphosis No Yes Reduced mobility Occasionally Very often Pain Common Very common Reduced chest expansion No Common Radiological \201 ndings: Hyperostosis Yes Yes Sacroiliac joint erosions No Yes ALLossi \201 cation Yes \200\224common No PLLossi \201 cation Yes \200\224occasionally No Syndesmophytes No Very common Erosive enthesitis No Very common Non-erosive enthesitis Very common Common ALL, anterior longitudinal ligament; PLL, posterior longitudinal ligament. CHAPTER 8 The spondyloarthridities 294 Table 8.6 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) The assessment comprises 6 questions with an analog score answer of 0 ( \200\230none \200 \231) to 10 ( \200\230very severe \200\231) for each on a 10 cm scale. The questions are: 1. How would you describe the overall level of fatigue/tiredness you have experienced? 2. How would you describe the overall level of AS neck, back or hip pain you have had? 3. How would you describe the overall level of pain/swelling in joints other than neck, back, or hips you have had? 4. How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure? 5. How would you describe the overall level of discomfort you have had from the time you wake up? 6. How long does your morning stiffness last from the time you wake up? (for this score the 10 cm scale is divided evenly so that 30 mins lies at 2.5 cm, 1 hr at 5 cm, 1 and a half h ours at 7.5 cm, and 2 or more hours at 10 cm). The score is calculated by adding each of the measures for question 1 to 4 to the mean of t he sum of questions 5 and 6, and then dividing the whole by 5. The maximum score therefore is 10. The treatment of ankylosing spondylitis \200 General principles include the following: patient education \200 exercise \200 physical therapy and hydrotherapy \200 avoid smo king \200 NSAIDs for spinal disease \200 self-help groups. Emphasis is placed on the need to maintain posture and physical activity. Extension exercises are important as the natural history of the disease is toward \202 exion and loss of height. Physical therapy and rehabilitation provide bene \201 t in the short term but it remains unclear about long-term bene \201 ts. Spa treatment has b een shown to improve function for up to 9 months, with subsequent reduction in health resou rce use. Spa therapy is expensive and not widely available. \200 Fatigue may be a major c oncern, hampering exercise. In some cases, low-dose amitriptyline at night may ameliorate this problem. For the majority of patients, NSAIDs remain the treatment of choice. The majority will be t aking diclofenac or naproxen. Indomethacin was widely used but less so now because of its G I side effects. Preliminary data suggest that continuous use of NSAIDs (such as ketoprofen or celecoxib) slow radiographic progression of disease over a 2-year period. Com pared to non-selective NSAIDs, COX-2 ANKYLOSING SPONDYLITIS 295 inhibitors have fewer GI side effects and are equally effective at providing symptomatic re lief, but have fallen out of favor. Celecoxib is the only COX-2 still available in the Unit ed States. Sulfasalazine has been shown in meta-analysis to be ef \201 cacious when compared with pla cebo for peripheral joint disease only. However, improvement in symptoms and quality of lif e is often not dramatic and sulfasalazine has a small role to play, perhaps mainly in perip heral in \202 ammatory disease. Mixed results have been found with MTX. A Cochrane meta-analysis concluded that there is in suf \201 cient evidence to support the use of MTX. Bene \201 t may be limited to patients with peripheral disease. Joint in \202 ammation can be managed in acute, severe cases with intra-articular corticosteroids, as can dactylitis and tendonitis by local steroid in \201 ltration. Care should be taken injecting around tendons, as rupture can occur. Injection a round the Achilles tendon is not recommended. Systemic steroids are rarely used, though the re is evidence that low dose IV therapy can produce a short-lived improvement in symptoms. In \202 iximab, etanercept, adalimumab, and golimumab have been used in spinal and periphe ral disease with good results in clinical outcome measures. Inevitably some patients requir e joint replacement, most commonly at the hip. Response to such surgery is usually excellen t provided there are not major periarticular contractures secondary to ankylosis. Surgery for spinal deformity is possible but carries considerable anesthetic and surgical risk and should be carried out in specialist centers. Topical steroid eye drops should be used to treat uveitis. If the symptoms persist for more than 3 days an ophthalmological opinion should be sought. In \202 iximab and etanercept have been used to treat resistant iritis. Any associated psoriasis, in \202 ammatory bowel disease, or concern over reactive in \202 ammation secondary to an infection should be treated accordingly. There is no treatment for pulmonary \201 brosis associated with AS. Given the added poten tial concern of reduced chest expansion, patients should be advised not to smoke in an atte mpt to avoid further lung disease. Nevertheless, it is important to remember that the majority of patients have some level of functional impairment due to their disease, and many will lead full, active lives. CHAPTER 8 The spondyloarthridities 296 Psoriatic arthritis Epidemiology and clinical features \200 The association between psori asis and an in \202 ammatory arthropathy is well-recognized. It may affect any peripheral joint as well as the axial skeleton and sacroiliac joints. Epidemiological studies support the notion of a distinct disease as opposed to the random \201 nding of coexisting common conditions such as psoriasis and RA. Psoriasis affects 1 \200\2232% of the population, and 10 \200\22340% of these develop arthritis. The condition affects women and men equally, usually between the ages of 20 \200\22340. RF can be present in up to 10% of patients with psoriasis, 90% remaining seronegative, and most patients with psoriatic arthritis run a benign course. In about 20% of cases there is a chronic, progressive, and deforming arthropathy with an often asymmetrical pattern, including distal interphalangeal joint involvement, and speci \201 c radiological features that can distinguish it from RA. Nail lesions may be the only clinical feature that can identify patients with psoriasis who are destined to develop arthritis. These lesions occur in 90% of patients with psoriatic a rthritis (PsA) and in 40% of patients with psoriasis alone. A comparison between PsA and RA (see Chapter 5) is made in Table 8.7. The joint symptoms most commonly occur after the dia gnosis of psoriasis, but may predate or occur simultaneously in a minority. The clinical patterns of psoriatic arthritis are: distal, involving the distal interphalangeal joints (DIP) \200 asymmetric oligoarthritis \200 symmetrical polyarthritis, indistinguishable from RA \200 spondylarthropathy \200 arthritis mutilans Arthritis mutilans is a classic (but uncommon) manifestation of psoriatic arthritis. Bone resorption leads to collapse of the soft tissue in the digits, cr eating \200\234telescoping \201 ngers. \200\235 This can also be seen in severe RA. The radiological features associated with PsA which help to differentiate it from RA include: \200 absence of juxtaarticular osteoporosis \200 DIP disease \200 \200\234whittling \200\235 (lysis) of terminal phalanges \200 asymmetry \200 \200\234pencil-in-cup \200\235 deformities \200 ankylosis \200 periostitis \200 spondylitis. The patterns of arthritis may change over time in > 60% of patients. \200 It is not clear though if the patterns of disease have any prognostic signi \201 cance and the changes and prognosis are variable. The frequency of spinal involvement can vary between 2% in isolated back disease, to 40%, when associated with peripheral arthritis. PSORIATIC ARTHRITIS 297 Table 8.7 Comparison of psoriatic arthritis and rheumatoid arthritis Feature Psoriatic arthritis Rheumatoid arthritis Sex ratio F = M F > M Symmetry of joint disease Less common Very common DIP involvement Common Uncommon Spine involvement Common Uncommon Skin/nail changes Common Uncommon Enthesopathy Common Uncommon Ankylosis Common Uncommon Osteopenia Uncommon Common Dactylitis, swelling of the whole \201 nger, occurs in over one-third of patients. Tenosynovitis and enthesitis are also common, particularly at the plantar fascia insertion and Achilles tendon. Hyperuricemia, probably related to high skin cell turnover, is not uncommon. In patients with psoriatic arthritis, the possibility of gout should be kept in m ind. The 2006 CASPAR criteria for the classi \201 cation of psoriatic arthritis are sometimes u sed to establish the diagnosis of psoriatic arthritis, although they were not designed for this purpose (Table 8.8). The CASPAR criteria allow subjects to be classi \201 ed as having psoriatic arthritis based on the presence of dactylitis or enthesitis in the absence of true arthriti s. The CASPAR criteria also allow subjects to be classi \201 ed as having psoriatic arthri tis with only a family history of psoriasis, as long as other criteria are met. Treatment of PsA \200 This should include the treatment of the skin as well as the joints and many patients are also under the care of a dermatologist. Patient education, physiotherapy, occupational therapy, and surgery all have a role to play akin to that already described above for RA and AS. Initial treatment in mild cases is with NSAIDs, adding a DMARD if in \202 ammation and joint damage persist. The reader is referred to the section on the Ev aluation and Treatment of Rheumatoid Arthritis in Chapter 5 for further details on speci \201 c agents. Sulfasalazine and le \202 unomide may be used with some effect; there are a necdotal reports of \200\234 \202 ares \200\235 of skin psoriasis with hydroxychloroquine , glucocorticoid taper, and TNF-inhibitors. The most commonly used agent is MTX; it also ca n have a dramatic effect on the skin disease. Sulfasalazine may also be ef \201 cacious. O nly physical therapy, NSAIDs, TNF inhibitors, and direct steroid injections appear to be co nsistently effective for axial arthritis. CHAPTER 8 The spondyloarthridities 298 Oral and IM steroids should be avoided, but intra-articular steroids may be used. Psoriatic plaques are colonized by bacteria, and injection through a plaque sh ould be avoided for fear of introducing infection. Steroid taper may lead to a \202 are o f pustular psoriasis. Patients with severe and unresponsive disease can be offered cyclosporine A and retinoids. Etanercept, in \202 iximab, adalimumab, and golimumab are FDA approved for the treatment o f PsA and have positive effects on skin as well as joint disease. The doses required to tre at psoriatic arthritis may be higher than the doses used to treat RA. Patients treated with etanercept 50 mg twice weekly, adalimumab 50 mg weekly, or adalimumab 40 mg weekly have a higher response rate than patients treated with standard RA doses, although the higher dose s may be accompanied by a higher risk of complications, such as infection. Table 8.8 The Classi \201 cation Criteria for Psoriatic Arthritis (CASPAR) (cid:2) 3 points required to meet criteria for psoriatic arthritis 2 points: A personal or family history of psoriasis 1 point: Typical psoriatic nail dystrophy 1 point: Absence of rheumatoid factor (RF) 1 point: Dactylitis (on exam or by history) 1 point: Juxta-articular bone formation on plain radiographs Taylor W, et al. Classi \201 cation criteria for psoriatic arthritis: development of new c riteria from a large international study. Arthritis Rheum 2008; 54: 2665 \200\2232673. This page intentionally left blank CHAPTER 8 The spondyloarthridities 300 Reactive arthropathy Clinical presentation \200 Reactive arthritis is an aseptic in \202 ammatory arthritis triggered by an infectious agent outside the joint. Spondyloarthritis can be de \201 ned as reactive if urethritis/cervicitis (sexually transm itted reactive arthritis or SARA) or diarrhea (gut associated reactive arthritis or GARA) a re present. The features of the spondyloarthridities can vary in the reactive subgroup from one patient to another, and in the same patient at any given time in the course of the dis ease. The onset of reactive arthritis may be acute, with fever, weight loss, and diffuse polyarti cular involvement. More often, however, there is limited joint synovitis and a low-grade, o r absent, fever. Mucocutaneous features include painless balanitis circinata of the glans penis, and pustular psoriasis of the palms or feet (keratoderma blennorhagica); these can be associated with a more severe outcome. \200 Conjunctivitis is observed early. Uve itis is less frequent early in disease, often occurring in recurrent disease and between ep isodes of arthritis. Acute diarrhea may precede the musculoskeletal symptoms by up to 1 month. The GI symptoms m ay be so mild that they are ignored by the patient and often the provoking agent has cleare d from the gut before the joint symptoms arise. Several triggering agents have been isolate d from stools and these include Shigella , Salmonella , Clostridium , and Yersinia . Chroni c diarrhea does not appear to be associated with reactive arthritis. However, the demarcati ons can be blurred and some patients may have in \202 ammatory bowel-associated arthropath ies, or silent in \202 ammatory lesions that appear to manifest as \200\230reactive-like \200\231 and are best described as undifferentiated spondyloarthropathy. Urethritis, prostatitis, or cervicitis may be present at prompt suspicion of infection. Rig orous investigation is required to ensure pathogenic mycoplasma and ureaplasma are identi \201 ed and eradicated. The most common nongonococcal urethritis is due to Chlamydia. Recurrent or repeated infections do not always lead to a recurrence of arthritis and may occur in the absence of further sexual intercourse. There are some imp ortant differential diagnoses outside the spondyloarthridities that include HIV-associated arthritis, Lyme disease, parvovirus arthropathies, and Beh et \200\231s disease (see Cha pter 18). Diagnosis and treatment of reactive arthritis \200 The in \202 ammatory nature of the co ndition can be con \201 rmed by the presence of an elevated ESR and CRP. For therapeutic d ecisions in some cases, but mainly for epidemiological purposes, many tests can be done loo king for a causative agent. Most screens are negative and in this sense there is merit in j ust taking a close history and limited investigation rather than a full diagnostic work-up. If required, the clinician should request stool, urine, and blood cultures, urethral and v aginal swabs, and aspirate a swollen joint looking for cells, crystals, REACTIVE ARTHROPATHY 301 and infection. It may be helpful to enlist the expertise of colleagues in infectious diseas es for the assessment of sexually acquired infections. \200 The use of monoclonal antibod ies, or DNA and RNA hybridization, in the search for products of triggering agents, is limi ted to research purposes. Likewise, tests for detecting antibodies to bacteria have no spec i \201 c place in current clinical practice and do not have a predictive value on outcome. In the early stages of disease there are no radiological signs except in a very small numbe r of cases where changes in the sacroiliac joints may be seen and probably predate presenta tion. There is no speci \201 c cure. NSAIDs and local corticosteroid injections are the mainstay of therapeutic intervention. If symptoms persist longer than 6 months and there is clinica l evidence of ongoing synovitis and joint destruction then a disease-modifying agent such a s sulfasalazine, MTX, or TNF inhibitors should be considered. Taking account of all symptoms, the bulk of patients are in complete remission at the end o f 2 years, the majority within 6 months. The metatarsophalangeal joints and the heel often remain sites of persistent pain, and balanitis and keratoderma may persist, acting as marke rs of potential poorer prognosis. Other factors that may be predictive of poor outcome incl ude oligoarthritis of the hip, persistently elevated ESR, poor response to NSAIDs, dactylit is, and involvement of the lumbosacral spine. Aseptic urethritis and early conjunctivitis resolve quickly and spontaneously. Antibiotic therapy will clear underlying infections but this may not have an y effect on the duration of disease. Uveitis should be treated in the usual way with topical steroid drops and a referral to an ophthalmologist if there has been no response within 3 days. Patient education, particularly in the context of food hygiene and of prevention of exposur e to sexually acquired infection, is important. Contact tracing is vital in cases of sexual ly transmitted infection. CHAPTER 8 The spondyloarthridities 302 Enteric arthropathy Clinical presentation \200 The arthropathies of ulcerative colitis an d Crohn \200\231s disease have many similarities and the combination of peripheral and axial skeletal disease, enthesopathies, mucocutaneous, and ocular disease \201 ts neatly into the diagnostic realm of the spondyl oarthropathies. The exact pathology is unknown, but is thought to be due to impairment of the gut-mediated immunity and increased bowel permeability, allowing bacteria to pass through the bowel wall into the circulation. Mono- or asymmetrical oligoarthritis can be coincident with the onset of bowel disease or a rise during the course of the disease. There is a close association between exacerbation of bowel and peripheral joint disorders, and enteropathic arthritis (EA) tends to remit after removal of diseased bowel tissue. The knees and ankles are most commonly involved. In contrast to peripheral arthritis, sacroiliitis is not clearly associated with either the onset or exacerbation of the bowel disease and may be present for years prior to the onset of colitis or ileitis. Other nonarticular features to look for include: uveitis (in about 10%) \200 erythema nodosum \200 pyoderma gangrenosum \200 aphthous stomatitis. Arthropathy associated with in \202 ammatory bowel disease often improves with treatment o f the bowel symptoms. Intra-articular steroids, sulfasalazine, and MTX can be used in resis tant cases. NSAIDs should be used with caution as they can cause a \202 are of Crohn \200 \231s disease. Anti-TNF- A therapies used in treatment of Crohn \200\231s disease may also improve joint symptoms. Enteric arthropathy may exist in patients with minimal or no gut symptoms. Presence of an asymmetric arthritis associated with oral ulcerations or erythema nodosum should trigger a colonoscopy with blind biopsies to evaluate for the presence of in \202 ammatory bowel disease or Beh et \200\231s disease. UNDIFFERENTIATED SPONDYLOARTHRITIS 303 Undifferentiated spondyloarthritis Epidemiology and clinical presentation \200 Undifferen tiated spondyloarthritis is one of the most common spondyloarthridities, with a prevalence approaching 2%. Undifferentiated spondyloarthritis is used to describe patients who meet some of the clinic al features associated with the spondyloarthridities, but not enough to be classi \201 ed as one of the diseases described in this chapter. Using ESSG criteria, the diagnosis of undifferentiated spondyloarthritis may be entertained if the patient has one of the following two major criteria (in the absence of psoriasis, i n \202 ammatory bowel disease, or other evidence of one of the other forms of spondyloarth ritis): \200 In \202 ammatory back pain (onset <40 years old, insidious onset, symptoms (cid:4) 3 months, morning stiffness, improvement with exercise) Asymmetric synovitis (predominantly of the lower extremities) \200 Most of these patients are young men with in \202 ammatory lower back pain and/or an asymmetric oligoarthritis, and are HLA-B-27 positive. Dactylitis and extra-articular manifestations are less common am ong patients with this diagnosis. In general, radiographic evidence of sacroiliitis is mild. Clear evidence of sacroiliitis o n plain radiographs may indicate that the patient is evolving towards a diagnosis of ankylo sing spondylitis. A small number of patients may eventually develop clear evidence of psori atic arthritis. Diagnosis and treatment \200 Diagnosis is based on clinical features. Although most patie nts are HLA-B27 positive, in \202 ammatory markers may not be elevated, and cannot be used to exclude this diagnosis. Early identi \201 cation and treatment of patients who are destined to evolve into ankylosing spondylitis may be key to preventing morbidity associated with this disease. How to identify patients at highest risk for progression, however, is not clear. MRI typically demonstrates evidence of sacroiliitis before changes on visible on plain radi ographs, and may be useful for identifying which patients merit treatment with TNF- A inhib itors. For other patients, non-steroidal anti-in \202 ammatory agents remain the mainstay of ther apy. Methotrexate, sulfasalazine, and le \202 unomide may also play a role in the treatmen t of undifferentiated spondyloarthritis, although this has not been well established. CHAPTER 8 The spondyloarthridities 304 SAPHO Epidemiology and clinical presentation \200 SAPHO is a relapsing and remitting illn ess that primarily affects young adults. The prevalence of SAPHO is unknown, but may be aro und 1/10,000. The acronym describes the components of this disease: Synovitis, Acne, Pustulosis, Hyperost osis, and Osteitis. Older names for this syndrome include: \200 Acne arthritis \200 Pus tulotic arthro-osteitis \200 Sternoclavicular hyperostosis \200 Acne-associated spondyl oarthropathy Palmoplantar pustulosis is the most common skin \201 nding in SAPHO, and is found in over half of patients with this diagnosis. Other skin lesions associated with SAPHO include pso riasis vulagris, severe acne, psoriasis, hidradenitis suppurativa, acne conglobata, pyoderm a gangrenosum, and Sweet \200\231s syndrome. It is important to note, however, that skin le sions may be subtle: 16% of patients may have no skin \201 ndings at all. Hyperostosis, particularly of the sternoclavicular joints, is likely the result of recurren t osteitis. This osteitis is aseptic, and does not respond to antibiotics. That said, 15% f o patients with chronic recurrent multifocal osteomyelitis have infection with Proprionibac terium acnes, although the signi \201 cance of this \201 nding is not completely clear. The synovitis most commonly affects the anterior chest wall; 63% of patients will have invo lvement of the steronoclavicular joints. Peripheral joint involvement may be either symmetr ic or asymmetric. \200 Because of its association with psoriasis, SAPHO is often classi \201 ed as a form of spondyloarthropathy. It is also interesting to note that 10% of patien ts with SAPHO are HLA-B27 positive. Diagnosis and treatment \200 This syndrome has four major subtypes: Osteoarticular manifestations of severe acne \200 Osteoarticular manifestations of palmop lantar pustulosis \200 Hyperostosis with or without dermatosis \200 Chronic recurrent m ultifocal osteomyelitis involving the axial or peripheral skeleton, with or without dermatosis To diagnose SAPHO, infectious causes of osteomyelitis must be excluded. Plain radiographs of the anterior chest wall may demonstrate lytic lesions and sclerosis in the sternoclavicular heads. Involvement of the sternoclavicular heads may be more clearly demonstrated with a Technitium-99 bone scan. Treatment includes non-steroidal anti-in \202 ammatory agents as a \201 rst line therapy. Methotrexate is the most commonly used steroid sparing SAPHO 305 agent, although low-dose glucocorticoids, methotrexate, sulfasalazine, colchicine, and cycl osporine have all been used. Intravenous pamidronate may be particularly effective for the treatment of osteitis. TNF- A blockade with etanercept and in \202 iximab has also been us ed with some success. The overall prognosis is felt to be better than that associated with the other spondyloarthridities, although this is dif \201 cult to prove. CHAPTER 8 The spondyloarthridities 306 Spondyloarthridities in childhood Epidemiology and clinical presentation \200 This umbrel la term covers a heterogeneous group of diseases associated with HLA B27 that affect children under the age of 16 and produce a spectrum of symptoms in adulthood. The disease group includes: enthesitis and arthritis syndrome \200 juvenile ankylosing spondylitis \200 juvenile re active arthritis \200 juvenile psoriatic arthritis(JPsA) \200 arthritis associated with in \202 ammatory bowel disease Using the ILAR classi \201 cation, this spectrum of diseases is called enthesitis-related arthritis (ERA). Incidence is estimated at 1.44 per 100,000 children. Prevalence has increased over the last 30 years. IgM RF and antinuclear antibodies are not found. 90% patients will be HLA B27 positive. The diagnosis is often more dif \201 cult in childhood as symptoms of back pain and radiol ogical changes are uncommon. The diagnosis rests more often on the presence of lower limb l arge joint arthritis associated with enthesopathy, acute uveitis, psoriasis, or bowel patho logy, and may be dif \201 cult to separate from JIA. The reader is referred to Chapter 9 f or a description of the classi \201 cation criteria for childhood arthropathies. Apart from an increased incidence of peripheral disease and rare axial symptoms, juvenile o nset spondyloarthridities resemble the adult forms. This lack of early axial disease may le ad to initial misdiagnosis as oligoarticular JIA. The Rome and New York criteria for the diagnosis of adult AS have not been validated in chi ldren; nevertheless, a small proportion of children \201 t these criteria and is consider ed to have juvenile AS. Approximately 5 \200\2238% of children attending rheumatology clini cs have AS. This compares with 75% having JIA. Juvenile AS commonly presents with lower lim b large joint arthritis (often knees and ankles) with the early course often episodic. It a lso appears to differ from adult AS in the precocious destruction of the hip joint. The con dition is reported more often in men than women, and 50% of cases go on to develop AS in ad ult life. Enthesitis and arthritis syndrome usually affects the feet and can be disabling. The disease is usually episodic, but some cases are chronic, resulting in bony e rosions and joint ankylosis. Over 70% patients with enthesitis syndrome will ful \201 ll d iagnostic criteria for AS after 5 \200\22310 years from onset. Childhood reactive arthritis and enteropathic arthropathy are essentially similar to adult disease. SPONDYLOARTHRIDITIES IN CHILDHOOD 307 JPsA \200 JPsA is de \201 ned in the ILAR criteria as either arthritis in the presence o f psoriasis, or arthritis and at least 2 of: \200 dactylitis \200 nail abnormalities (pit ting or onycholysis) \200 family history of psoriasis con \201 rmed by a dermatologist i n at least