Musculoskeletal Manifestations

Introduction

There is a predilection for the inflammation to affect sites where the tendons and ligaments attach to the bones (entheses), especially in the sacroiliac (SI) joints and the spinal column, in patients with ankylosing spondylitis/ axial spondyloarthritis (AS/axSpA). The symptoms usually begin insidiously during the late teens or early twenties, and is twice as common in males than females. The presenting clinical manifestations during the early stage of the disease can often be nonspecific and wide ranging. Pain resulting from inflammation of the SI joints is commonly the earliest symptom, usually dull in character, difficult to localize, felt initially deep in the gluteal area, and sometimes intermittent and alternating from side to side (the so-called “alternating buttock pain”) before it becomes bilateral.

A teenager or a young adult presenting with chronic back pain and stiffness that worsens with prolonged inactivity is a typical early presentation. Data from developed countries indicate that the average age of onset is around 24 years and approximately 15% have disease onset in childhood (before age 16), but this percentage may be as high as 40% in some developing countries. The average age at onset does not differ significantly among males and females, but the onset is significantly at a younger age in HLA-B27–positive patients vs those who lack this gene.

The inflammatory process gradually progresses over months and years to involve the lumbar spine, causing chronic low back pain and stiffness that worsens late at night and early morning or after prolonged inactivity, but is alleviated to a variable extent with physical activity or exercise, hot showers, or use of nonsteroidal anti-inflammatory drugs (NSAIDs). The features suggesting the inflammatory nature of the patient’s back pain, as proposed by Calin and colleagues, include insidious onset before the age of 45 years, with a duration of at least 3 months, worsening with inactivity, improving with physical exercise and being associated with spinal stiffness on waking up in the morning. Most recently, inflammatory back pain (IBP) has been defined by having at least four of the following five characteristics:

• Insidious onset
• Onset before age 40 years
• Pain at night (with improvement upon getting up)
• Improvement with exercise
• No improvement with rest.

According to the best trade-off, if at least four of these five parameters are fulfilled, this definition has 80% sensitivity and 72% specificity. Although IBP and stiffness are very important presenting clinical symptoms that suggest presence of AS/axSpA, this definition of IBP is not sensitive enough because approximately 20% of patients with AS/axSpA would lack symptoms that meet this definition. Moreover, they are also not specific enough because about 28% of control groups (such as patients with mechanical back pain) report symptoms that meet this definition of IBP. Occasionally, back pain may be absent or too mild to impel the patient to seek medical care.

Some patients may complain only of back stiffness, fleeting muscle aches, or musculo-tendinous tender spots. These symptoms may become worse on exposure to cold or dampness, and some of these patients may be misdiagnosed with fibromyalgia. Sometimes pain and stiffness in the mid-thoracic or the cervical region or anterior chest wall pain and tenderness may be the initial symptom rather than the more typical low backache. This may be a more common presentation in women. Moreover, women tend to have a slower disease progression or have atypical presentation, and therefore they may not be as easily diagnosed as men. However, this delay in diagnosis of AS in women, as in men, is decreasing as a result of greater awareness of this disease by many healthcare providers.

It is rare for the disease to begin after the age of 45, but there is a small percentage of patients with well-documented late-onset AS. However, there are many patients with young age of onset but may get diagnosed when they are more than 45 years old. Some patients may have had minimal symptomatic progression or had been pain-free for long periods of time, and may finally present with back pain due to other causes such as osteoporosis-related microfractures or extra-articular manifestations, such as acute anterior uveitis (AAU). Enthesitis most frequently occurs at sites that are subject to greater physical stress. Thus some patients can present with pain and tenderness at the insertions of the plantar fascia and Achilles tendon into the calcaneum, or patellar tendon insertion into the tibial tubercle. Others can have pain and tenderness over vertebral spinal processes, iliac crest, anterior chest wall, ischial tuberosities, greater trochanters and sometimes patella and tibial tubercles.

Pain and tenderness of the anterior chest wall due to enthesitis at costosternal junctions and inflammation of the manubriosternal junction, and sternoclavicular and costoclavicular joints can occur early in the disease course. Some of these patients present with chest pain that is usually accentuated on coughing or sneezing and at times may even mimic symptoms of atypical angina or pericarditis. Others may give a history of having complained of chest pain to a physician before AS was diagnosed. Thus a variety of healthcare professionals (such as primary care physicians, physiatrists, orthopedists, chiropractors, podiatrists, dermatologists ophthalmologists and gastroenterologists, as well as other medical and surgical specialists) first see such patients and the diagnosis is often missed or markedly delayed.

Tenderness and stiffness of the paraspinal muscles often accompany the inflammation of the axial skeleton. The inflammatory process in the axial skeleton may also involve the discovertebral junctions and the facet joints, as well as the costovertebral, and costotransverse joints of the spine and the paravertebral ligamentous attachments. With disease progression, there is a gradual loss of spinal mobility, along with flattening of the lumbar spine, and exaggerated thoracic spine kyphosis. Involvement of the costovertebral and costotransverse joints leads to a gradual decrease in chest expansion, with resultant greater diaphragmatic breathing. Some patients may present with an inability to expand the chest fully on inspiration, which is normally at least 5 cm in healthy young individuals at the level of the xiphisternum, or they may complain about exertional dyspnea. In patients with severe progressive disease, there is a gradual limitation of neck mobility due to progressive syndesmophyte formation and facet joint fusion, with resultant forward stooping of the neck.

Enthesitis may be detected radiographically but not in early stages, while Doppler ultrasonography and MRI, on the other hand, can detect early inflammatory changes even before they appear on conventional radiographs. Radiographic evidence of sacroiliitis and spinal ankylosis may progress more slowly in women than in men, but functional outcome, as analyzed by studying activities of daily living, is similar. However, when it comes to pain and the need for drug therapy, female patients tend to be worse off, possibly because of slower (or a relatively incomplete) progression of spinal fusion which results in a decrease in inflammatory pain, or the problem of any concomitant fibromyalgia-like symptoms. Measures of spinal mobility, such as modified Schober’s test and lateral flexion, are important in the assessment of AS, but are often late findings.

Sometimes the first symptoms may result from involvement of the hip and shoulders joints, the so-called girdle joints. They are affected in at least one third of AS patients over the course of their disease. Hip joint involvement is usually bilateral and gradual in onset; the pain is usually felt in the groin, although some patients may feel it in the knee or the front of the thigh on the same side. It has been correlated with early age at onset of AS and is an indicator for a bad prognosis. There is a gradual destruction and thinning of the joint cartilage and it is accompanied by gradual limitation of joint motion.

However, some degree of contracture of the hip joints is not uncommon at later stages of the disease even without hip joint involvement, giving rise to a characteristic rigid gait, with the patient keeping the knees bent a little in an attempt to maintain an erect posture. There is usually some atrophy and weakness of thigh and buttock muscles due to their lack of use in patients with advanced disease. Involvement of the hip joints in a patient with a rigid spine, including the neck, is potentially more crippling and can lead to greater disability, but total hip joint replacement can minimize those limitations. Shoulder joint involvement is generally mild, with some limitation of range of motion.

Involvement of the peripheral joints other than the hips and shoulders in primary AS (without associated psoriasis or IBD) is uncommon, and may affect knees more so than other joints. It is rarely persistent or destructive and tends to resolve without any residual joint deformity. However, more prominent and/or widespread peripheral joint involvement, tendinitis, bursitis, tenosynovitis, and dactylitis are more often observed in patients with concomitant IBD or psoriasis. Inflammation can also affect structures adjacent to the joints, such as tendons and bursae, resulting in tendonitis and bursitis. Inflammation of the temporo-mandibular joint is uncommon, and may cause pain, tenderness, or some limitation in fully opening the mouth.

Osteoporosis

Patients with AS have osteoproliferative lesions in the axial skeleton, and yet they are also more likely to develop spinal osteoporosis, which can contribute to progressive spinal kyphosis as a result of anterior vertebral body wedge compressions. Spinal osteoporosis is caused in part by the ankylosis and lack of mobility, but it can also occur relatively early in the disease, possibly due to high disease activity with increased level of proinflammatory cytokines and an alteration in vitamin D metabolism, causing increased bone resorption. Clinical detection of osteoporosis is discussed in Imaging. The new bone formation is controlled by the Wnt/β‐catenin signaling, and Dickkopf‐1 (Dkk‐1) is an inhibitor of the Wnt pathway. Platelets are a major source of Dkk‐1 in humans. A recent study reported a lower concentration of Dkk‐1 in serum of axSpA patients in comparison to controls. Furthermore, the expression of Dkk‐1 was significantly reduced in axSpA platelets both at the transcriptional and protein level. The authors suggest that dysfunction of the megakaryocyte‐blood platelet axis might be responsible for reduced serum Dkk‐1 in axSpA patients. which might translate into new bone formation.

Patients with a rigid osteoporotic spine are prone to spinal fracture with relatively minor physical trauma, which may not even be recalled by some patients. Therefore spinal fracture needs to be ruled out in any patient with advanced AS who has new onset of neck or back pain, even in the absence of a history of trauma. Transverse displaced fractures of the neck are associated with significant morbidity and mortality and can result in quadriplegia. Patients with AS have a 5-fold higher risk of clinical spine fracture and a 35% increased risk of non-vertebral fracture.

Other Forms of SpA

This book focuses on AS/axSpA, and therefore there are no detailed sections on psoriatic arthritis (PsA), enteropathic spondyloarthritis (SpA) and reactive arthritis. They have been discussed in other publications by the authors. We provide here a brief discussion about related forms of SpA, including some of their extraskeletal manifestations (Table 6-1). Among patients suffering from psoriasis, more than 10% (range 5% to 42% among various reports) have associated inflammatory arthritis, including sacroiliitis and or spondylitis. Enteropathic arthritis is a major extraintestinal manifestation of IBD, present in up to 25% of such patients. Axial disease (sacroiliitis alone or with classic clinical and radiographic features of primary AS) symptoms do not fluctuate with bowel disease activity. But peripheral arthritis tends to correlate with flare-up of IBD, especially in the case of ulcerative colitis.

Reactive arthritis (ReA) is an aseptic inflammatory arthritis that follows an episode of urethritis/cervicitis, diarrhea, or both. Inflammation may also appear occur at extra-articular sites, such as the eyes, skin and mouth. It classically occurs within 4 weeks after a triggering infection of the gut or the genitourinary tract, although many patients may not recall such a history. Chlamydia trachomatis, Yersinia and Salmonella are the most relevant pathogens triggering ReA in developed countries.

Juvenile or childhood-onset SpA refers to a group of SpA characterized by peripheral arthritis and enthesitis (therefore sometimes called enthesitis related arthritis [ERA] or seronegative enthesitis and arthritis [SEA] syndrome) more frequently than inflammatory back pain. It can be viewed on a continuum with adult onset SpA, and sacroiliitis may be more common than expected based on their symptoms.

The term “undifferentiated SpA” is used when the patients, quite often children, have a limited form or early stage of SpA that does not meet the criteria for AS or the above-mentioned forms of “differentiated” SpA. It encompasses disorders such as isolated enthesitis or dactylitis, seronegative oligoarthritis or polyarthritis (usually involving the lower extremities) and absence of psoriasis, IBD, or genitourinary tract inflammation. It is often HLA-B27–associated and can later evolve into one of the “differentiated” forms of SpA.