Spondyloarthropathies RAJESH K. KATARIA, D.O., and LAWRENCE H. BRENT, M.D. Albert Einstein Medical Center, Philadelphia, Pennsylvania

The include ankylosing , reactive (including Reiter’s syndrome), , inflammatory bowel disease–associated , and undifferentiated spondyloarthropathy. These diseases are linked by their association with the HLA-B27 gene and by the presence of as the basic pathologic lesion. Additional clinical features include inflammatory , , and extra-articular manifestations such as and skin rash. The history and physical examination are the major diagnostic tools, although radiographic evidence of is helpful. Therapeutic options include nonsteroidal anti-inflammatory drugs, , , and - inhibitors. Early recognition and appropriate treatment can help to limit disability. (Am Fam 2004;69:2853-60. Copyright© 2004 American Academy of Family .)

he spondyloarthropathies are a or spondylitis may be seen on radiographs of diverse group of inflammatory the and lumbar spine. arthritides that share certain Although the spondyloarthropathies are genetic predisposing factors grouped together, they display distinct clinical and clinical features1 (Table features. It is likely that an interplay among T1).1-3 Their most characteristic feature is genetic, environmental, and immunologic inflammatory back pain.4 Enthesitis, another factors is responsible for the various clinical characteristic feature, involves manifestations of these diseases. Infection at sites where tendons, ligaments, or with an unknown organism or exposure to capsules attach to (Table 2). Enthesitis an unknown antigen in a genetically suscep- is believed to be the primary lesion in the tible patient (HLA-B27–positive) is hypoth- spondyloarthropathies, whereas synovitis is esized to result in the clinical expression of a the main lesion in . Dac- spondyloarthropathy.5 This article reviews the tylitis (inflammation of an entire digit), com- diagnosis and treatment of the most common monly termed “sausage digit,” also occurs in spondyloarthropathies. the spondyloarthropathies and is thought to arise from joint and tenosynovial inflamma- tion. The prevalence of ankylosing spondylitis, Although diagnostic criteria for the spon- the most common spondyloarthropathy, is 0.1 dyloarthropathies have been developed for to 0.2 percent in the general U.S. population research purposes, the criteria rarely are used (possibly as high as 1 percent in certain groups) in clinical practice. Diagnosis is based pri- and is related to the prevalence of HLA-B27. marily on the history and physical examina- Ankylosing spondylitis most often affects white tion. There are no specific diagnostic tests for males between 15 and 40 years of age.6 spondyloarthropathies. Supporting labora- The inflammatory back pain in ankylosing tory findings include absence of rheumatoid spondylitis typically has an insidious onset factor, elevation of the erythrocyte sedimen- and a dull quality, and the pain radiates into tation rate (ESR) or C-reactive protein (CRP) the gluteal regions. Back pain is worse in the level, and presence of anemia of chronic morning, improves with activity, and has a disease. HLA-B27 testing is of limited value. nocturnal component.6 The typically is inflammatory Over time, axial arthritis can progress from See page 2745 for defi- (more than 2,000 white blood cells per mL, the sacroiliac , gradually ascending to nitions of strength-of- with a predominance of neutrophils), but this involve the cervical spine. Limited spinal recommendation labels. finding is nonspecific. Evidence of sacroiliitis mobility results from spinal deformities such

Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. TABLE 1 Features of the Most Common Spondyloarthropathies

Ankylosing (including IBD-associated Features spondylitis Reiter’s syndrome) Psoriatic arthritis spondyloarthropathy

Prevalence 0.1% to 0.2% 0.1% 0.2% to 0.4% Rare Age at onset Late teens to early Late teens to early 35 to 45 years Any age adulthood adulthood Male-to-female ratio 3:1 5:1 1:1 1:1 HLA-B27 90% to 95% 80% 40% 30% Sacroiliitis Frequency 100% 40% to 60% 40% 20% Distribution Symmetric Asymmetric Asymmetric Symmetric Syndesmophytes Delicate, marginal Bulky, nonmarginal Bulky, nonmarginal Delicate, marginal Peripheral arthritis Frequency Occasional Common Common Common Distribution Asymmetric, lower limbs Asymmetric, lower limbs Asymmetric, any joint Asymmetric, lower limbs

Enthesitis Common Very common Very common Occasional Dactylitis Uncommon Common Common Uncommon Skin lesions None Circinate balanitis, Erythema nodosum, keratoderma blennorrhagicum Nail changes None Onycholysis Pitting, onycholysis Clubbing Ocular conditions Acute anterior uveitis Acute anterior uveitis, Chronic uveitis Chronic uveitis conjunctivitis Oral conditions Ulcers Ulcers Ulcers Ulcers Cardiac conditions Aortic regurgitation, Aortic regurgitation, Aortic regurgitation, Aortic regurgitation conduction defects conduction defects conduction defects Pulmonary features Upper lobe fibrosis None None None Gastrointestinal None Diarrhea None Crohn’s disease, ulcerative conditions colitis Renal conditions , IgA nephropathy Amyloidosis Amyloidosis Nephrolithiasis Genitourinary Prostatitis Urethritis, cervicitis None None conditions

IBD = inflammatory bowel disease. Information from references 1 through 3.

as flattening of the lumbar , exaggera- develop arthritis in the hips and shoulders, tion of the thoracic , and hyperexten- frequently early in the course of the dis- sion of the cervical spine. ease. Other peripheral joints usually become Although Schober’s test is nonspecific, it is affected later. The lower extremities most useful for measuring spinal mobility. The test often are involved in an asymmetric fashion. is performed by marking the patient’s back Enthesitis is common in patients with anky- over the L5 spinous process (between the pos- losing spondylitis. Inflammation at the Achilles terior superior iliac spines) and 10 cm above tendon and calcaneal insertions this point. The patient then is asked to bend is particularly common and manifests as heel forward. The distance between the two marks pain. Like arthritis, enthesitis typically is aggra- should increase by 5 cm or more in normal vated by rest and improved with activity. persons. An increase of less than 5 cm sug- Extra-articular features of ankylosing spon- gests decreased range of motion of the lumbar dylitis can involve almost any organ system. spine. Constitutional symptoms include , Some patients with ankylosing spondylitis anorexia, and mild fever. Anterior uveitis is

2854-AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 69, NUMBER 12 / JUNE 15, 2004 TABLE 2 Common Sites of Enthesitis in Patients with Spondyloarthropathies

Achilles tendon insertion on the calcaneus Plantar fascia insertion on the calcaneus Patellar tendon insertion on the tibial tubercle Superior and inferior aspects of the patella Metatarsal heads Base of the fifth metatarsal Spinal ligament insertions on the vertebral bodies

FIGURE 1. Radiograph of the pelvis in a patient with ankylosing spondylitis and bilat- eral sacroiliitis. The radiograph shows joint the most frequent extra-articular manifesta- space narrowing and bony sclerosis around tion, occurring in 25 to 30 percent of patients.7 the sacroiliac joints (arrows). The uveitis usually is acute, unilateral, and recurrent. Eye pain, red eye, blurry vision, disease is diagnosed less frequently in women, , and increased lacrimation are because axial symptoms are less severe. Periph- presenting signs. Cardiac manifestations eral arthritis may be more prominent in include aortic and mitral root dilatation, with women. regurgitation and conduction defects. Fibrosis Pharmacologic treatment of ankylosing may develop in the upper lobes of the in spondylitis begins with nonsteroidal anti- patients with longstanding disease. inflammatory drugs (NSAIDs), which have Although there is no laboratory test to diag- been shown to provide rapid relief of inflam- nose ankylosing spondylitis, the HLA-B27 matory back pain. A positive response to gene has been found to be present in about NSAID is helpful in diagnosing anky- 90 to 95 percent of affected white patients in losing spondylitis.8 central Europe and North America.5 How- Second-line agents such as sulfasalazine ever, a positive HLA-B27 assay is nonspecific, (Azulfidine) are used when patients do not because the antigen is found in 8 to 10 per- respond to NSAIDs or are unable to tolerate cent of white persons and in up to 2 percent these agents. One meta-analysis demonstrated of black persons.5 Furthermore, only 1 to 2 that sulfasalazine is safe and effective in the percent of HLA-B27–positive persons develop short-term treatment of ankylosing spon- ankylosing spondylitis.5 The ESR rate and dylitis.9 The meta-analysis of five random- CRP level are elevated in 50 to 70 percent of ized double-blind, placebo-controlled trials patients, but the elevations generally do not (RCTs)7 showed statistically significant and correlate with disease activity.7 clinically important improvement in patients Radiographic features of ankylosing spondy- treated with sulfasalazine, although two sub- litis include bilateral symmetric sacroiliitis, sequent trials failed to show efficacy for the with initial sclerosis progressing to erosive drug.10,11 Sulfasalazine appears to be effective changes and total or fusion of the in alleviating peripheral arthritis in patients sacroiliac joints (Figure 1). Spinal involvement with ankylosing spondylitis but is less effective because of enthesitis initially is seen as squar- in patients with axial disease. ing of the vertebral bodies, then osteitis at the Although not well studied, methotrexate vertebral margins (Figure 2) and, eventually, (Rheumatrex) may be beneficial in patients ossification of the annulus fibrosus, with the with prominent peripheral arthritis.12 Oral formation of delicate marginal syndesmoph- in conventional dosages are ytes in a gradually ascending pattern that occa- of little value in the treatment of ankylosing sionally results in the classic “bamboo spine” spondylitis, but intra-articular (Figure 3). Syndesmophytes are due to ossifica- injections can provide rapid and sustained tion of the annulus fibrosus, which eventually relief in isolated inflamed joints.8 Intravenously may bridge the intervertebral space. administered pamidronate (Aredia) appears to The diagnosis of ankylosing spondylitis have a modest effect on disease activity.13 should be suspected in young patients who Several trials14-16 have evaluated the effi- present with inflammatory back pain. The cacy of the tumor necrosis factor- (TNF-)

JUNE 15, 2004 / VOLUME 69, NUMBER 12 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN-2855 FIGURE 2. Radiograph of the lumbar spine in FIGURE 3. Radiograph of the lumbar spine in a patient with ankylosing spondylitis. Inflam- a patient with ankylosing spondylitis. Ossifi- mation at the site of insertion of the annulus cation of the annulus fibrosus in the lumbar fibrosus has resulted in osteitis of the anterior spine has resulted in the formation of mar- vertebral margins, also called “shining cor- ginal syndesmophytes in a gradually ascend- ners” (arrow). ing pattern (“bamboo spine”).

inhibitors (Enbrel) and weeks after a genitourinary or gastrointestinal (Remicade) in patients with ankylosing spon- tract infection. Causative organisms include dylitis. Data from the trials clearly indicate (among others) Chlamydia, Ureaplasma, Shi- that these agents are effective in treating the gella, Salmonella, Yersinia, and Campylo- inflammatory symptoms of ankylosing spon- bacter species.19 dylitis. The TNF- inhibitors also have poten- The arthritis tends to be oligoarticular, tial as disease-modifying agents.17,18 The U.S. preferentially affecting the joints of the lower Food and Drug Administration has approved extremities. Onset is typically acute: within a etanercept for use in the treatment of ankylos- few days, two to four joints become painful ing spondylitis. and swollen in an asymmetric distribution. Nonpharmacologic therapy is an impor- Weight loss and temperatures of up to 38.8°C tant adjunct to drug therapy. Interventions (102°F) have been recorded during the acute include patient education, outpatient physical phase.19 Enthesitis is common, especially in therapy, a home exercise program (including the heel. Dactylitis and inflammatory back spinal extension exercises), and proper pos- pain also are common. turing. Inpatient rehabilitation may be neces- Radiographic features of reactive arthri- sary in selected patients. tis include enthesitis with periosteal reaction (Figure 4), asymmetric sacroiliitis, and discon- Reactive Arthritis and Reiter’s Syndrome tinuous spondylitis with bulky nonmarginal Reactive arthritis is an aseptic arthritis that syndesmophytes.20 is triggered by an infectious agent located out- Extra-articular manifestations are essential side the joint. Reiter’s syndrome, one of the in supporting the diagnosis of reactive arthri- earliest described forms of reactive arthritis, tis. Conjunctivitis is present in up to 50 per- is a clinical triad of nongonococcal urethritis, cent of patients and can develop at any time conjunctivitis, and arthritis. during the course of the disease. This feature Reactive arthritis usually begins one to four is reported to be more common in patients

2856-AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 69, NUMBER 12 / JUNE 15, 2004 Spondyloarthropa- thies

FIGURE 4. Radiograph of the heel in a patient with Reiter’s syndrome. The radiograph shows a periosteal reaction at the plantar fascia insertion (black arrow) and early erosion at the insertion (white arrow) on the calcaneus. with reactive arthritis subsequent to genito- urinary or Shigella infection. As in ankylosing spondylitis, uveitis most often is acute, unilat- eral, and recurrent.20,21 Urethritis classically is a sterile variant, although Chlamydia trachomatis and Urea- FIGURE 5. Keratoderma blennorrhagica in a plasma urealyticum have been isolated in many patient with Reiter’s syndrome. patients with reactive arthritis. The urethritis can range from asymptomatic to severe with accompanying prostatitis. In women with with NSAIDs. Sulfasalazine has been shown reactive arthritis, cervicitis usually is marked to be effective in patients with chronic reactive by vaginal discharge. arthritis.22 Intra-articular corticosteroid injec- Acute diarrhea frequently is a presenting tions can be effective in controlling disease in manifestation when reactive arthritis develops individual joints. after Shigella, Yersinia, or Salmonella infec- Because of the underlying bacterial etiology tion. The diarrhea precedes the appearance in reactive arthritis, there has been much dis- of musculoskeletal symptoms by up to one cussion about the possible role of antibiotic month.19 therapy in patients with the disease. Antibi- Oral ulcers are common and may be pain- otic therapy has not been effective in several less. Circinate balanitis, a painless erythema- trials.23,24 tous lesion of the glans penis, is present in An association between certain spondy- about 20 percent of male patients with reac- loarthropathies (reactive arthritis, psoriatic tive arthritis.21 arthritis, undifferentiated spondyloarthrop- Keratoderma blennorrhagicum, a manifes- athy) and human immunodeficiency virus tation of Reiter’s syndrome, is characterized infection has been noted, particularly in sub- by the development of hyperkeratotic lesions Saharan Africa.25 The patients have tended to on the palms of the hands or the soles of the have more severe disease, and the increased feet (Figure 5). Lesions often begin as clear prevalence is thought to be due to poor avail- vesicles on an erythematous base and progress ability of effective antiretroviral therapy. to macules, papules, and nodules. The lesions are indistinguishable from those of pustular Psoriatic Arthritis psoriasis.19 Psoriasis affects up to 1 to 2 percent of the Although reactive arthritis usually has a general U.S. population, and psoriatic arthri- self-limited course of three to 12 months, tis has been reported in as many as 20 percent symptomatic treatment is warranted. Up to of patients with psoriasis. In the majority 50 percent of patients have recurrent bouts of of cases, skin manifestations precede joint arthritis, and 15 to 30 percent develop chronic involvement, although the reverse occurs in arthritis or sacroiliitis.20 Treatment begins 15 to 20 percent of cases.26

JUNE 15, 2004 / VOLUME 69, NUMBER 12 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN-2857 FIGURE 6. Psoriatic arthritis: oligoarticular pat- FIGURE 7. Psoriatic arthritis: arthritis muti- tern. Note prominent involvement of the left lans. wrist and right thumb (arrows). and can occur bilaterally. Radiographs in patients with psoriatic There are five recognized patterns of pso- arthritis demonstrate an erosive arthritis, with riatic arthritis: an oligoarticular type (four or frequent DIP joint involvement and pencil- fewer joints affected); a polyarticular type (five in-cup changes because of marked resorption or more joints affected); a pattern with pre- of bone (Figure 9). Other findings, including dominant distal interphalangeal (DIP) joint enthesitis with periosteal reaction, sacroiliitis, involvement; ; and psoriatic and spondylitis, are similar to those in patients spondylitis. The oligoarticular pattern accounts with reactive arthritis. for more than 70 percent of cases27 (Figure 6). Treatment of psoriatic arthritis is directed at Psoriatic arthritis usually is asymmetric, both the skin and joint manifestations. A vari- and distal joints often are affected. These ety of topical , including corticoste- features distinguish psoriatic arthritis from roids, retinoids, and ultraviolet-light therapy, rheumatoid arthritis. Clinical presentations can be used for the skin disease. NSAID ther- range from mild, remitting arthritis to highly apy, the initial treatment for joint manifesta- destructive disease (Figure 7). The severity of tions, improves swelling and tenderness. Oral the arthritis usually does not correlate with corticosteroid therapy occasionally is useful the extent of skin involvement. in the treatment of generalized disease, and If a diagnosis of psoriatic arthritis is being intra-articular corticosteroid injections can considered, the skin should be examined care- control localized joint disease. Second-line fully for psoriatic lesions. In addition to mani- agents include methotrexate, sulfasalazine, festing in typical sites (e.g., extensor surface of cyclosporine (Sandimmune), and TNF- the knee), psoriasis can be present as a small inhibitors.1,28,29 Etanercept has been shown to patch in the scalp, ears, anal cleft, perineum, control disease activity and inhibit progres- or umbilicus. Nail lesions, including pitting sion of joint destruction.30 and onycholysis, occur in more 80 percent of patients with psoriatic arthritis27 (Figure 8). In Spondyloarthropathy Associated psoriatic arthritis, uveitis tends to be chronic with Inflammatory Bowel Disease Spondyloarthropathy occurs in up to 20 The Authors percent of patients who have inflammatory 2 RAJESH K. KATARIA, D.O., is an associate with Cumberland Medical Associates, P.A., bowel disease (IBD). The association occurs Millville, N.J. After graduating from the University of and of New more often in patients with Crohn’s disease Jersey School of Osteopathic Medicine, Stratford, Dr. Kataria completed an internal than in those with . In some medicine residency at Kennedy Memorial Hospital, also in Stratford, and a rheumatol- ogy fellowship at Albert Einstein Medical Center, Philadelphia. patients, arthritis manifests before clinical bowel disease. LAWRENCE H. BRENT, M.D., is head of the division and director of the Einstein Arthritis Center, Albert Einstein Medical Center, Philadelphia. Dr. Brent Typically, the arthritis affects the lower received his medical degree from Jefferson Medical College of Thomas Jefferson extremities in an asymmetric fashion. Onset University, Philadelphia, and completed an residency and a rheuma- usually is abrupt, and the arthritis has a tology fellowship at Thomas Jefferson University Hospital. He also completed a post- doctoral research fellowship sponsored by the Arthritis Foundation at the University migratory pattern. The arthritis generally sub- of Alabama at Birmingham. sides in six to eight weeks, although recur- Address correspondence to Lawrence H. Brent, M.D., Einstein Arthritis Center, 5501 rence is common, and 10 percent of patients Old York Rd., Korman 103, Philadelphia, PA 19141 (e-mail: [email protected]). develop chronic arthritis. In up to 20 percent Reprints are not available from the authors. of affected patients, IBD-associated spondy- loarthropathy manifests as a spondylitis that

2858-AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 69, NUMBER 12 / JUNE 15, 2004 FIGURE 9. Radiograph of the hands in a patient with arthritis mutilans. The radio- graph shows severe destructive arthritis with a pencil-in-cup deformity (arrow). The defor- mity occurs when the distal head of a bone FIGURE 8. Nail pitting in a patient with psori- becomes pointed and the adjacent joint sur- atic arthritis. face becomes cup-like because of erosions. is indistinguishable from idiopathic ankylos- Patients with undifferentiated spondyloar- ing spondylitis. Exacerbations of peripheral thropathy generally have a good prognosis and arthritis and IBD tend to coincide, whereas often respond well to NSAID therapy. Treat- axial disease is independent of IBD activity.2 ment of patients with more severe disease is Extra-articular manifestations of IBD-asso- similar to that for ankylosing spondylitis. ciated spondyloarthropathy include uveitis, Further information on the spondyloar- which is usually bilateral, and chronic skin thropathies is available on the following Web lesions, such as erythema nodosum and pyo- sites: http://www.arthritis.org, http:// www. derma gangrenosum. Less common features rheumatology.org, and http://www. spondy- include clubbing, , amyloidosis, and litis.org. granulomatous disease of bone and joint. The treatment of IBD-associated arthritis is Strength of Recommendations slightly more complex than the treatment of Strength of other spondyloarthropathies. NSAIDs should Key clinical recommendations recommendation References be used cautiously, because they can exac- erbate the bowel disease.2 Sulfasalazine has Clinical criteria supported by laboratory C 4, 5, 7 been effective in the treatment of IBD and tests, synovial fluid analysis, and radiographs help to establish the 31 arthritis. Data on azathioprine (Imuran) presence of spondyloarthropathies. and methotrexate therapy in patients with Initial management begins with NSAIDs C 8 severe disease also have been promising.2 Treatment with TNF- inhibitors may have Sulfasalazine (Azulfidine) may be an effective B 9-11 second-line agent that provides short-term a beneficial effect on the associated arthritis in relief. patients with IBD.3 Early trials indicate that tumor necrosis B 17,18 factor- inhibitors such as etanercept Undifferentiated Spondyloarthropa- (Enbrel) and infliximab (Remicade) are thy effective in treating inflammatory The term “undifferentiated spondyloar- symptoms. thropathy” is used to describe manifestations Despite the possibility of a bacterial etiology B 23 of a spondyloarthropathy in patients who do in reactive arthritis, antibiotic therapy has not meet criteria for any of the well-defined been ineffective. spondyloarthropathies. Over time, a small Second-line treatment of psoriatic arthritis B 1, 28-30 proportion of these patients develop a well- (after NSAIDs have failed) includes systemic corticosteroids, methotrexate (Rheumatrex), defined spondyloarthropathy. However, most sulfasalazine, cyclosporine (Sandimmune), patients have less specific symptoms, including and tumor necrosis factor- inhibitors. inflammatory back pain, unilateral or alter- nating buttock pain, enthesitis, dactylitis and, NSAID = nonsteroidal anti-inflammatory drug. occasionally, extra-articular manifestations.

JUNE 15, 2004 / VOLUME 69, NUMBER 12 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN-2859 Spondyloarthropathies

The authors indicate that they do not have any treating ankylosing spondylitis: a randomized, con- conflicts of interest. Sources of funding: none trolled trial. Arthritis Rheum 2003;48:3230-6. reported. 16. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicen- REFERENCES tre trial. Lancet 2002;359:1187-93. 1. Gladman DD. Psoriatic arthritis. Rheum Dis Clin 17. Braun J, Sieper J, Breban M, Collantes-Estevez E, North Am 1998;24:829-44. Davis J, Inman R, et al. Anti-tumour necrosis factor 2. De Keyser F, Elewaut D, De Vos M, De Vlam K, alpha therapy for ankylosing spondylitis: interna- Cuvelier C, Mielants H, et al. Bowel inflammation tional experience. Ann Rheum Dis 2002;61(suppl and the spondyloarthropathies. Rheum Dis Clin 3):iii51-60. North Am 1998;24:785-813,ix-x. 18. Braun J, Pham T, Sieper J, Davis J, van der Linden S, 3. Gladman D. Spondyloarthropathies. In: Lahita R, Dougados M, et al. International ASAS consensus Weinstein A, eds. Educational review manual in statement for the use of anti-tumour necrosis fac- rheumatology. 2d ed. rev. New York: Castle Con- tor agents in patients with ankylosing spondylitis. nolly Graduate Medical, 2002:1-26. Ann Rheum Dis 2003;62:817-24. 4. Van der Linden S, van der Heijde D. Ankylosing 19. Amor B. Reiter’s syndrome. Diagnosis and clinical spondylitis. Clinical features. Rheum Dis Clin North features. Rheum Dis Clin North Am 1998;24:677- Am 1998;24:663-76,vii. 95,vii. 5. Van der Linden S, van der Heijde D. Ankylosing 20. Yu DT, Peng TF. Reiter’s syndrome. In: Ruddy S, spondylitis. In: Ruddy S, Harris ED Jr, Sledge CB, Harris ED Jr, Sledge CB, eds. Kelley’s Textbook of eds. Kelley’s Textbook of rheumatology. 6th ed. rheumatology. 6th ed. Philadelphia: Saunders, Philadelphia: Saunders, 2001:1039-54. 2001:1055-70. 6. Calin A, Porta J, Fries JF, Schurman DJ. Clinical his- 21. Lau CS, Burgos-Vargas R, Louthrenoo W, Mok tory as a screening test for ankylosing spondylitis. MY, Wordsworth P, Zeng QY. Features of spondy- JAMA 1977;237:2613-4. loarthropathies around the world. Rheum Dis Clin 7. Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. North Am 1998;24:753-70. Ankylosing spondylitis: an overview. Ann Rheum 22. Clegg DO, Reda DJ, Weisman MH, Cush JJ, Vasey Dis 2002;61(suppl 3):iii8-18. FB, Schumacher HR Jr, et al. Comparison of sul- 8. Dougados M, Dijkmans B, Khan M, Maksymowych fasalazine and placebo in the treatment of reactive W, van der Linden S, Brandt J. Conventional treat- arthritis (Reiter’s syndrome). A Department of Vet- ments for ankylosing spondylitis. Ann Rheum Dis erans Affairs Cooperative Study. Arthritis Rheum 2002;61(suppl 3):iii40-50. 1996;39:2021-7. 9. Ferraz MB, Tugwell P, Goldsmith CH, Atra E. Meta- 23. Yli-Kerttula T, Luukkainen R, Yli-Kerttula U, Mot- analysis of sulfasalazine in ankylosing spondylitis. tonen T, Hakola M, Korpela M, et al. Effect of J Rheumatol 1990;17:1482-6. a three month course of ciprofloxacin on the 10. Dougados M, van der Linden S, Leirisalo-Repo M, outcome of reactive arthritis. Ann Rheum Dis Huitfeldt B, Juhlin R, Veys E, et al. Sulfasalazine in 2000;59:565-70. the treatment of spondyloarthropathy. A random- 24. Leirisalo-Repo M. Prognosis, course of disease, and ized, multicenter, double-blind, placebo-controlled treatment of the spondyloarthropathies. Rheum study. Arthritis Rheum 1995;38:618-27. Dis Clin North Am 1998;24:737-51,viii. 11. Clegg DO, Reda DJ, Weisman MH, Blackburn WD, 25. Mijiyawa M, Oniankitan O, Khan MA. Spondy- Cush JJ, Cannon GW, et al. Comparison of sulfasala- loarthropathies in sub-Saharan Africa. Curr Opin zine and placebo in the treatment of ankylosing Rheumatol 2000;12:281-6. spondylitis. A Department of Veterans Affairs Coop- 26. Gladman DD, Pahman P. Psoriatic arthritis. In: erative Study. Arthritis Rheum 1996;39:2004-12. Ruddy S, Harris ED Jr, Sledge CB, eds. Kelley’s 12. Sampaio-Barros PD, Costallat LT, Bertolo MB, Neto JF, Textbook of rheumatology. 6th ed. Philadelphia: Samara AM. Methotrexate in the treatment of anky- Saunders, 2001:1071-80. losing spondylitis. Scand J Rheumatol 2000;29:160- 27. Moll JM, Wright V. Psoriatic arthritis. Semin Arthri- 2. tis Rheum 1973;3:55-78. 13. Maksymowych WP, Jhangri GS, Fitzgerald AA, 28. Combe B, Goupille P, Kuntz JL, Tebib J, Liote F, LeClercq S, Chiu P, Yan A, et al. A six-month ran- Bregeon C. Sulphasalazine in psoriatic arthritis: a domized, controlled, double-blind, dose-response randomized, multicentre, placebo-controlled study. comparison of intravenous pamidronate (60 mg Br J Rheumatol 1996;35:664-8. versus 10 mg) in the treatment of nonsteroidal 29. Spadaro A, Riccieri V, Sili-Scavalli A, Sensi F, Taccari antiinflammatory drug–refractory ankylosing spon- E, Zoppini A. Comparison of cyclosporin A and dylitis. Arthritis Rheum 2002;46:766-73. methotrexate in the treatment of psoriatic arthritis: 14. Gorman JD, Sack KE, Davis JC Jr. Treatment of a one-year prospective study. Clin Exp Rheumatol ankylosing spondylitis by inhibition of tumor necro- 1995;13:589-93. sis factor alpha. N Engl J Med 2002;346:1349-56. 30. Ory P, Sharp JJ, Salonen D, Rubenstein J, Mease 15. Davis JC Jr, van der Heijde D, Braun J, Dougados PJ, Kivitz AJ, et al. Etanercept (ENBREL) inhibits M, Cush J, Clegg DO, et al. Recombinant human radiographic progression in patients with psoriatic tumor necrosis factor receptor (etanercept) for arthritis [Abstract]. Abstracts of the American College of Rheumatology 66th annual meeting

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