Insertional tendonitis, such as plantar fasciitis, dactylitis, or Achilles tendinitis, may be painful and recurrent, but they do not leave serious sequelae apart from occasional new bone formation (plantar spur).

Although physical signs may be minimal in the early stages of AS, tenderness and spasm of the paraverterbral muscles, and limitation of motion of the lumbar spine, may occur. Direct pressure over involved joints and tendons may elicit pain.

Genitourinary disease in AS patients can include chronic prostatitis, which appears to be more frequent in patients with AS than in normal patients or patients with RA [236].

Renal involvement with clinical manifestations is a rare complication of AS in spite of recognized pathologic changes detected in electron microscopy and immunoßuorescence studies [237, 238]. Renal damage may occasionally be caused by amyloidosis after many years of disease [239] or by IgA nephropathy [240].

Extraarticular Systemic Manifestations

Although extraarticular systemic manifestations are uncommon in patients with AS, many body systems may become affected, especially after years of active disease. Constitutional symptoms include fever, malaise, anorexia, and weight loss.

Cardiovascular involvement is more frequent in patients with severe spondylitis, marked peripheral arthritis, and prominent systemic manifestations [232]. Aortic incompetence, conduction abnormalities (including complete heart block, causing AdamsÐStokes disease), cardiomegaly, ascending aortitis, and pericarditis are the primary abnormalities that may occur in AS patients [233, 234]. Vasculitis in AS is predominanlty a large-artery arteritis.

Ankylosing spondylitis pulmonary disease is characterized by progressive Þbrotic changes of the upper lobes of the lungs, with eventual cyst formation and parenchymal destruction. These lesions may become invaded with Aspergillus and form a mycetoma [232]. Death may follow massive hemoptysis.

Neurological manifestations in AS patients are most often related to subluxations, fracture dislocations, or cauda equina syndrome [232]. Atlantoaxial subluxation and cervical spine fracture dislocation are the most frequent problems. Cauda equina syndrome, occurring in the later stages of the disease, is due to lumbar central midline disk herniation causing paralysis of the sacral roots; its diagnosis requires emergency neurosurgery (laminectomy). It presents with leg or buttock pain with sensory and motor impairment, and bowel and bladder dysfunction. Multiple sclerosis may be associated with AS more often than would be expected by chance alone [235].

6.1.3.3 Ocular Manifestations

Although anterior uveitis is the most common ocular manifestation in AS, scleritis may occasionally occur. Other ocular problems include conjunctivitis and the complications of uveitis and/or scleritis, such as cataract, seclusion of the pupil, iris bombe, secondary glaucoma, or macular edema. Episcleritis does not occur in patients with AS more commonly than in normal control populations.

Anterior Uveitis

Anterior uveitis, the most common extraarticular manifestation of AS, occurs in approximately 25% of patients either before the onset of the disease or at some point thereafter [232, 241]. Conversely, AS is the most common systemic condition associated with anterior uveitis in men: 17Ð31% of men with anterior uveitis have AS [229]. The clinical association between anterior uveitis and AS becomes strengthened by the Þnding that 50% of patients with anterior uveitis, and 90% of patients with anterior uveitis and a rheumatic disease, are HLA-B27 positive [229]. The presence of anterior uveitis does not correlate with the severity of the spondylitis but may be more frequent in patients with peripheral involvement. It is typically unilateral but may become bilateral. The characteristic symptoms of anterior uveitis in AS are acute onset of pain, photophobia, redness, and blurred vision, although it may be mild or even asymptomatic. The characteristic signs are prominent ciliary injection, Þne whitishgray keratic precipitates, and Þbrinous exudation in the anterior chamber that contributes to the formation of posterior synechiae. An underrecognized fact, which is clear from our experience

with a large number of patients with uveitis, is that AS HLA-B27 patients may develop a violent, explosive onset of anterior uveitis with hypopyon. The posterior segment is usually spared, although cystoid macular edema and, in our experience, retinal vasculitis may occasionally occur. Individual attacks of uveitis usually subside without residual visual impairment in 4Ð8 weeks, but they may recur over a period of years and become bilateral. Immediate ocular application of topical steroids and mydriatics by the patient as soon as the Þrst symptoms appear may abort the attack, provided he/she is soon seen by an ophthalmologist who can manage the attack and detect the ocular complications either of the treatment or disease (e.g., glaucoma, cataract, and macular edema). AS must always be considered in the differential diagnosis of anterior uveitis.

Scleritis

Scleritis may occur in AS with or without anterior uveitis. The reported incidence of AS in patients with scleritis ranges from 0.34 to 0.93% [122Ð124]. Occasionally, scleritis may be the initial manifestation of AS, preceding the disease by many years [196]. AS scleritis generally takes the form of mild-to-moderate diffuse anterior scleritis that, in spite of recurrences, never progresses to necrotizing anterior scleritis [122, 123, 196, 242]. Anterior uveitis may appear following the onset of scleritis, in which case it is impossible to know if the uveitis is a reßection of the associated scleritis, or represents an independent effect of the disease, or both. In our own series of 500 patients with scleritis, six patients had AS (1.2%). The mean age of the patients was 44 years (range, 28Ð57 years) and the scleritis was more common in men than in women (four males and two females). All patients had diffuse scleritis and three patients had bilateral scleritis. In four of the six patients, there was anterior uveitis-associated scleritis (sclerouveitis), and in three of those four patients there were previous episodes of anterior uveitis. Four of the six patients were diagnosed with AS several years before the onset of the scleritis and most of them had marked spondylitis, prominent peripheral arthritis, and cardiac conduction defects. Although scleritis may

precede the articular involvement of AS, it usually occurs after years of active AS disease, especially in patients with marked articular and extraarticular manifestations. Any patient who develops diffuse anterior scleritis after previous episodes of recurrent anterior uveitis should be examined for AS.

Episcleritis

Episcleritis is rare in AS. In our own series of 85 patients with episcleritis, there were three patients with AS: two female and one male. Two patients had simple episcleritis and one had nodular episcleritis. Episcleritis appeared an average of 6 years after the onset of the disease and responded well to oral nonsteroidal anti-inßammatory therapy. There were no corneal lesions, cataract, macular edema, or decrease in visual acuity.

6.1.3.4 Laboratory Findings

and Radiologic Evaluation

No laboratory test is diagnostic of AS. In most ethnic groups, the HLA-B27 gene is present in approximately 90% of patients. Serum alkaline phosphatase, serum creatinine phosphokinase, CRP, and ESR are frequently elevated in patients with AS. There appears to be little or no correlation between ESR and disease severity or prognosis. Mild anemia may be present. Elevated serum IgA levels are common. CICs may be found [243], but tests for rheumatoid factor, antiCCP, and ANAs are negative [232]. Synovial ßuid from peripheral joints in AS is nonspeciÞcally inßammatory. In cases with restriction of chest wall motion, decreased vital capacity and increased functional residual capacity are common, but airßow measurements are normal and ventilatory function is usually well-maintained.

Radiographic evaluation conÞrms the diagnosis by showing blurring of the subchondral bone plate, sclerosis, erosions, joint space narrowing, or ankylosis of sacroiliac joints (Fig. 6.11), characteristics of sacroiliitis, or erosions, vertebral squaring, syndesmophyte formation, ossiÞcation, or ankylosis of vertebral joints, characteristic of spondylitis. Bony erosions and osteitis may be seen at sites of osseous attachments of tendons and ligaments [232].