Co-morbidities and Extra-articular Manifestations of Spondyloarthropathy

Original Editor - Jess Bell Top Contributors - Jess Bell and Tarina van der Stockt

Introduction

Spondyloarthropathy is an umbrella term for a family of seronegative inflammatory conditions that have articular and extra-articular features. This page will explore some of the key co-morbidities, as well as extra-articular features experienced by patients with spondyloarthropathy. These co-morbidities and symptoms add to the burden of disease already experienced by spondyloarthropathy patients,[1] so early detection and general awareness of these conditions are essential.

Co-morbidities

Osteoporosis

Osteoporosis is defined as: “a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture."[2]

Osteoporosis is a recognised co-morbidity of many inflammatory conditions, including rheumatoid arthritis, juvenile idiopathic arthritis,[3] and spondyloarthropathy (in particular axial spondyloarthritis).[4] The reported prevalence rate of osteoporosis in axial spondyloarthritis varies from 11.7 to 34.4 percent.[5]

Axial spondyloarthritis causes a paradoxical situation in relation to bone metabolism - there is generalised bone loss, localised inflammatory bone resorption and new bone formation (e.g. syndesmophytes).[6]

The generalised bone loss may be due to systemic inflammation and disease activity. Increased inflammation and pro-inflammatory cytokines have also been connected to the development of secondary osteoporosis.[6] Steroid use may also be significant.[7]

Bone mineral density starts to decline in the early stages of axial spondyloarthritis.[4] 40 to 50 percent of patients with axial spondyloarthritis will have low bone mineral density six years after developing the condition.[3] Even patients with non-radiographic axial spondyloarthritis (i.e. no radiographic changes) have been demonstrated to have lower bone mineral density than patients with mechanical back pain.[3]

The bone loss and abnormal bone formation typical of axial spondyloarthritis can result in syndesmophytes, peri-vertebral bone formation, ankylosis of the zygapophyseal joints, abnormal bone formation in the ligamentous system, and in severe cases, complete fusion of the spine.[3] This osteoproliferation means that dual-energy x-ray absorptiometry, which is usually used to measure bone density, can be inaccurate in these patients - i.e. it can create the appearance of normal bone mineral density even in cases where osteoporosis is present.[3]

The presence of osteoporosis in spondyloarthropathy is significant as it increases the risk of vertebral fracture.[4] The prevalence rate of fractures varies from 11 to 24.6 percent.[5] While exercise has been found to be beneficial for patients with axial spondyloarthritis,[8] physiotherapists must design programmes that are suitable for patients who have osteoporosis. Specific information about the physiotherapy management of osteoporosis is found here.

The following videos provide general background information on osteoporosis.

Cardiovascular Disease

Like many other rheumatic conditions, spondyloarthropathy is associated with an increased risk of cardiovascular disease.[1] Types of cardiovascular disease associated with spondyloarthropathy include:[11]

  • Structural heart disease
  • Conduction defects
  • Ischaemic heart disease

A study by Lauper and colleagues explored the incidence and prevalence of major adverse cardiovascular events in patients with different rheumatic conditions, including rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis, and found no difference in rates across diseases.[12] Thus, it appears that inflammation is responsible for the increased risk rather than specific disease processes.[12]

Physiotherapists should, therefore, consider cardiovascular risk when treating patients with potential or diagnosed inflammatory conditions. Management strategies might include:[1]

  • Supporting and promoting exercise (see below)
  • Reducing and managing hypertension

Modifiable risk factors such as smoking and diet are also areas which should be addressed by the multi-disciplinary team.[1]

Types of Exercise

There is strong evidence to suggest that endurance exercise and strength training can help to protect against cardiovascular disease.[13] Moreover, a study by Sveaas and colleagues found that high-intensity exercise improved disease activity and reduced cardiovascular risk factors in patients with active axial spondyloarthritis.[13] The exercise programme in this study followed the American College of Sports Medicine (ACSM) recommendations for maintenance and improvement of cardiorespiratory and muscular fitness:[13]

  • Patients were encouraged to exercise 40–60 minutes, three times a week
  • Sessions consisted of endurance and strength training
    • Endurance training was high-intensity interval training that lasted for 40 minutes
    • Strength training lasted 20 minutes and focused on external load for the major muscle groups (six exercises, eight to ten repetitions maximum, two to three sets)

Depression

Depression often affects patients with chronic conditions like axial spondyloarthritis.[14] The prevalence of depression has been found to range from 11 to 64 percent, with around 15 percent of patient with axial spondyloarthritis having at least a moderate level of depression.[14]

In patients with axial spondyloarthritis, depression has been shown to be inversely associated with age, and associated with functional impairment and more severe disease.[14]

Because depression is associated with an increased risk of disease severity and a reduction in functional ability, physiotherapists should consider mental health when working with patients who have spondyloarthropathy. It can be useful to ask questions about the patient’s level of coping and his or her mood. Validated questionnaires such as the Patient Health Questionnaire-9 can be beneficial.[1] Depression is discussed in more detail here.

[15]

Reduced Physical Activity

A key consideration alongside these three co-morbidities is reduced physical activity. There is a growing evidence base to support the use of exercise therapy in the management of spondyloarthropathy.[16] It has been found to improve physical function, disease activity and chest expansion, as well as helping to decrease pain, improve stiffness, spinal mobility and cardiorespiratory function.[17]

Despite these advantages, patients with spondyloarthropathy, particularly axial spondyloarthritis are less physically active than the general population. Even patients who are active, are not typically exercising at recommended levels.[1]

The European League against Rheumatism (EULAR) states that exercise programmes should include four key areas:[18]

  • Strength
  • Cardiovascular
  • Flexibility
  • Neuromotor

Many patients with axial spondyloarthritis are only not engaging in such varied exercise programmes.[1] These patients have traditionally been advised to focus on hydrotherapy and flexibility exercises while strength training has been under-utilised.[16] Thus, physiotherapists need to consider the type of exercise, as well as the duration and intensity when designing exercise programmes for these patients.

Some exercise ideas are demonstrated in the following videos. Exercise management is discussed in more detail here.

Extra-Articular Manifestations

Acute Uveitis or Iritis

Acute anterior uveitis (AAU) is a form of eye inflammation and it is the most common extra-articular manifestation of axial spondyloarthritis,[21] with prevalence rates of between 21 and 33 percent.[22]

There is conflicting data about the influence of gender on this condition.[22] However, there are higher rates of AAU in individuals who are HLA-B27 positive and who have heel pain.[1][21] Prevalence also appears to increase with disease duration.[21] Only 12 percent of patients experienced a flare of uveitis within the first 5 years of their disease compared to 43 percent of patients with long-standing disease (i.e. 30+ years).[22] Prevalence rates also vary based on the type of spondyloarthropathy and across ethnicities.[22]

AAU is an ophthalmology emergency. Any patient presenting with this condition will need to see a specialist ophthalmologist within 24 hours of presentation.[1]

Signs and symptoms of AAU: [1]

  • Pain and / or redness in the eye due to inflammation of the iris
  • Most patients will have blurred vision
  • Floaters may be present (i.e. spots which appear in the visual field)
  • It is usually unilateral
  • Patients may report photophobia (i.e. an inability to look at light)

It is important to note that AAU can recur - around 50 percent of patients will have recurrent uveitis.[22]

[23]

Inflammatory Bowel Disease

The two main forms of inflammatory bowel disease (IBD) are:[1][24]

  1. Chron’s disease, which affects the entire gastrointestinal tract
  2. Ulcerative colitis (UC), which affects the colon only

Chron’s disease and UC are lifelong, debilitating, inflammatory conditions that often require surgical and medical intervention.[24]

Signs and Symptoms

UC is strongly associated with rectal bleeding. This bleeding may occur in conjunction with abdominal pain, diarrhoea, and signs of systemic involvement (i.e. fever or anaemia).[24]

The clinical presentation of Chron’s disease is often more varied.[24] Typical symptoms of severe Chron’s disease are:[24]

  • Fever
  • Malaise
  • Anorexia
  • Weight loss
  • Abdominal pain
  • Frequent diarrhoea with rectal bleeding

The occurrence of spondyloarthropathy in patients with IBD ranges from between 17 and 39 percent.[24] Thus, spondyloarthropathy is the most frequent extra-intestinal manifestation in patients with IBD. In about 20 percent of patients, the inflammatory back pain may develop before IBD, but musculoskeletal symptoms are usually diagnosed after IBD has developed.[24] Axial spondyloarthritis has been associated with a more chronic, and active form of IBD.[25]

The prevalence of inflammatory bowel disease in patients with axial spondyloarthritis is around four percent, but this rises to between five and ten percent in patients who have radiographic axial spondyloarthritis.[1] Prevalence also increases in patients who are HLA-B27 positive.[25]

Clear communication between all members of the multi-disciplinary team, as well as an understanding of the relationship between inflammatory bowel disease and spondyloarthropathy can aid early referral and diagnosis of these conditions.[1]

Psoriasis

Psoriasis is an immune-mediated, genetic disease that affects the skin and / or joints.[26] It is characterised by the rapid buildup of skin cells, which can cause red flaky, inflamed plaques on the skin.[1] There are different forms of psoriasis and they are categorised by their phenotype. Types of psoriasis include:

  • Plaque psoriasis[27]
    • This is the most common type of psoriasis, making up nearly 90 percent of cases
    • On clinical observation, it appears as erythematous plaques, which have sharp boundaries and are covered with pearlescent squamae. The lesions are distributed symmetrically. They most frequently appear on the knees, elbows, scalp, and sacral region
  • Guttate psoriasis[27]
    • This type of psoriasis often occurs in children and young adults. Lesions tend to usually appear suddenly and have the appearance of small droplets or squamous psoriatic papules (although these are less common). They generally develop after streptococcal infections. They typically appear on the trunk, proximal parts of the extremities, face, and scalp
  • Inverse psoriasis[27]
    • Inverse psoriasis (or flexural psoriasis) occurs in skin folds. Because of friction and moisture in these areas, squamous lesions do not form and instead, lesions are bright red, symmetric, infiltrative, fissured plaques that have distinctive contours. This type of psoriasis is more common in people who are obese
  • Erythrodermic psoriasis[27]
    • In erythrodermic psoriasis lesions affect nearly 80 percent of the body. Lesions are largely erythematous - typical papules and plaques do not retain their characteristic features and desquamation are not as distinct. Hypothermia can occur with erythrodermic psoriasis because of widespread vasodilatation. It can occur as an independent type of psoriasis, but most frequently, it develops as a complication of psoriasis vulgaris
  • Pustular psoriasis[27]
    • Different types of pustular psoriasis include:
      • Generalized pustular psoriasis (von Zumbusch type)
      • Impetigo herpetiformis
      • Localized pustular psoriasis
      • Palmoplantar pustular psoriasis (Barber type)
      • Acrodermatitis continua of Hallopeau

Psoriasis is, of course, more prevalent in patients who have psoriatic arthritis, but it affects approximately eight percent of patients with axial spondyloarthritis.[1]

[28]

As is clear from the various types of psoriasis discussed above, this condition is variable in terms of its morphology, distribution, severity and location of lesions.[1] Thus, it is important that clinicians ask their patients questions about their skin, including the scalp, behind the ears and on the extensor aspects of the arms, under the armpits (i.e. for inverse psoriasis) and across the abdomen (i.e. for guttate psoriasis).[1]

It is also useful to also ask about a family history of psoriasis, and any nail changes (pitting or nail onycholysis) as there have been links found between the nail and entheses.[1][29][30]

Peripheral Manifestations

Enthesitis

The enthesis is the area where tendons, ligaments and joint capsules attach to the bone.[31] While enthesopathies were previously believed to be localised, insertional disorders, advances in imaging have demonstrated that there are more widespread changes (i.e. in adjacent bone and surrounding soft tissue).[31] For instance, imaging studies of patients with lateral epicondylitis show that there are degenerative changes both at the common extensor origin entheses and in adjacent ligaments.[31] It has, therefore, been proposed that insertion sites should not be considered as focal attachments, but part of a wider “enthesis organ complex.” This complex helps to spread stress from the point of insertion away from the attachment site.[31][29]

Enthesitis is a common peripheral manifestation of spondyloarthropathy. It affects around 35 to 50 percent of patients with psoriatic arthritis and around 40 percent of patients with axial spondyloarthritis.[1] Enthesitis is likely linked to mechanical loading and may be more common in patients who are HLA-B27 positive. Mechanical loading appears to trigger a chain of inflammatory events, which are initially localised to the enthesis. However, this local inflammation then spreads and goes on to cause other issues, such as local synovitis and tenosynovitis.[1]

Ultrasound scans can be a useful diagnostic tool as they are able to reveal more diffuse, inflammatory changes at the enthesis than an x-ray can show. Doppler activity can help to distinguish between tendon and enthesitis changes. MRI is also able to detect enthesitis, although this method of imaging is more expensive than ultrasound.[1]

Dactylitis

Dactylitis is defined as diffuse swelling of the digits, and is colloquially known as sausage digits.[32] It tends to be asymmetrical[1] and occurs largely due to inflammation of the digital flexor tendon sheaths.[33]

It is a key feature of psoriatic arthritis, occurring in 40 percent of patients.[33] Its general prevalence across all spondyloarthropathies is 16 to 49 percent.[1] It also occurs in unrelated conditions such as sarcoidosis, gout, sickle cell disease, and various infections.[34] Dactylitis will recur in 44 percent of patients (often in the same digit) and it is more likely to affect the toes than the fingers.[33]

It often occurs early in the disease process and may be the only manifestation of psoriatic arthritis for months or even years before other symptoms develop.[1] Thus, when assessing patients who have previous or current dactylitis, it is important to consider if there is any other suspicion of spondyloarthropathy, particularly psoriatic arthritis.[1] Click here to view images of dactylitis.

Summary

There are various comorbidities and extra-articular or peripheral manifestations of spondyloarthropathy. Because of the varied nature of these conditions, diagnosis and classification can be difficult. However, utilising all members of the MDT can help to identify these patients early on.

Physiotherapists must consider the entire disease process when assessing and managing patients with spondyloarthropathy. These extra-articular manifestations often appear early in the disease process or in conjunction with other symptoms. Thus, it is important to ask questions about a patient's skin, eyes and gut, and if there has been any history of enthesitis and dactylitis. This can help to ensure that early signs of spondyloarthropathy are detected, which will ultimately result in better outcomes for patients.

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