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Rheumatology - Spondyloarthritis - Fast Facts | NEJM Resident 360

Spondyloarthritis is an inflammatory arthritis characterized by the following features:

• peripheral inflammatory arthritis (particularly an asymmetric oligoarthritis of large joints)

• enthesitis (inflammation of tendon insertion points)

• dactylitis (diffuse swelling of a digit due to diffuse tendon and joint inflammation) 

• uveitis

• inflammatory back pain (axial arthritis)

There are seven spondyloarthritides:

• Psoriatic Arthritis (PsA)

• Ankylosing Spondylitis (AS)

• Nonradiographic Axial Spondyloarthropathy (nrAxSpA)

• Inflammatory Bowel Disease (IBD)-Related Arthritis

• Reactive Arthritis

• Peripheral Spondyloarthritis (not covered in this guide)

• Juvenile Spondyloarthritis (not covered in this guide)

“Undifferentiated spondyloarthritis” is the term used for the rare cases when it is not possible to identify which type of spondyloarthritis a patient has. However, in general, the forms of spondyloarthritides can be differentiated on the basis of their clinical features as outlined in the table below:

Clinical Features of Various Forms of Spondyloarthritis

(Source: Psoriatic Arthritis. N Engl J Med 2017.)

Psoriatic Arthritis

Psoriatic arthritis (PsA) affects up to 30% of people with psoriasis. In nearly every case, there is a personal or family history of psoriasis; in some cases, the arthritis may precede the skin or nail changes associated with psoriasis. Psoriatic arthritis is characterized by the following features:

• asymmetric oligoarthritis of large joints

• symmetrical polyarthritis of proximal small joints (mimicking rheumatoid arthritis)

• distal interphalangeal joint arthritis (typically seen with nail psoriasis)

• axial spondyloarthritis

• arthritis mutilans (an aggressive, deforming arthritis with typical appearances of pencil-in-cup deformity on plain radiographs and eventually opera-glass deformity of the hands)

Clinical Features of Psoriatic Arthritis

Panel A shows the distal subtype of psoriatic arthritis, with adjacent onycholysis. Panel B shows the oligoarticular subtype. Panel C shows the polyarticular subtype. Panel D show arthritis mutilans, with telescoping of digits and asymmetric and differential involvement of adjacent digits. Panel E shows the spondylitis subtype. Panel F shows enthesitis of the Achilles’ tendon (arrow).
(Source: Psoriatic Arthritis. N Engl J Med 2017.)

Diagnosis

PsA is diagnosed clinically with supporting information from investigations. The common features of spondylarthritis are almost always present to some extent, with dactylitis and enthesitis frequently accompanying the arthritis. There is almost always a personal or family history of psoriasis, often including nail involvement.

In contrast with rheumatoid arthritis, PsA is not associated with rheumatoid factor (RF ) or anti-CCP antibodies; the detection of these antibodies in peripheral blood should raise the possibility of an alternative diagnosis, such as rheumatoid arthritis. For the purposes of clinical research, the Classification Criteria for Psoriatic Arthritis are commonly used and can be useful to clinicians.

The CASPAR Criteria*

To meet the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria, a patient must have inflammatory articular disease (joint, spine, or entheseal) with ≥3 points from the following five categories:

1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of psoriasis†

2. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis observed on current physical examination

3. A negative test result for the presence of rheumatoid factor by any method except latex

4. Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis recorded by a rheumatologist

5. Radiographic evidence of juxta-articular new bone formation, appearing as ill‐defined ossification near joint margins (but excluding osteophyte formation) on plain radiographs of the hand or foot

* The CASPAR criteria have specificity of 98.7% and sensitivity of 91.4% **for psoriatic arthritis among individuals with inflammatory musculoskeletal disease (peripheral arthritis, axial disease, or enthesitis).

**† Current psoriasis is assigned a score of 2; all other features are assigned a score of 1.
(Reference: Classification Criteria for Psoriatic Arthritis: Development of New Criteria from a Large International Study.  Arthritis Rheumatol 2006.)

Imaging

Plain radiographs: The typical abnormality seen on plain radiographs is a combination of bone loss (with eccentric erosions) and new bone formation (with ankyloses, enthesophytes, syndesmophytes, and periostitis). Other features that may be seen on plain radiograph include:

• bone formation at the site of periarticular structural insertions (such as tendons)

• periostitis at the lateral margins of the interphalangeal joints as a fluffy-appearing opacification

• pencil-in-cup deformities, seen with the arthritis mutilans presentation of PsA, characterized by tapering of one phalanx and central destruction of the opposite phalanx

• enthesitis, seen as a calcification in line with the tendon insertion on the bone

• dactylitis, observed as a swelling of soft tissue of the digit

• axial involvement, observed, when it occurs, asymmetrically in the sacroiliac joints

Treatment

The optimal treatment of psoriatic arthritis depends on the severity of the disease as follows:

• Mild disease: Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen may be all that is required.

• Moderate disease: Disease-modifying antirheumatic drugs (DMARDs) are often required, although they tend to be more effective for treatment of peripheral arthritis than spondylitis. Historically, weekly oral methotrexate has been used, though evidence for its benefits has not been clearly demonstrated in the published literature. Other DMARDs often used include leflunomide and sulfasalazine. In some cases of mild-to-moderate disease, apremilast (a phosphodiesterase type 4 inhibitor) may also be used.

• Severe disease: Treatment involves biologic DMARDs (bDMARDs), including monoclonal antibodies against tumor necrosis factor-alpha (TNF-alpha inhibitor; etanercept, adalimumab, golimumab, infliximab, certolizumab pegol), interleukin-17 (secukinumab, ixekizumab), interleukin-12/23 (ustekinumab), interleukin 23 (guselkumab), T-cell costimulation (abatacept), or small-molecule inhibitors, such as Janus kinase (JAK) inhibitors (tofacitinib).

Glucocorticoids are effective at treating inflammatory arthritis at all stages but tend to be reserved due to possible glucocorticoid-related adverse effects and because cessation of glucocorticoids can trigger a severe flare of psoriasis. When pustular psoriasis or erythroderma is present, glucocorticoids should be avoided. Intra-articular glucocorticoid injection therapy can be highly effective.

Skin disease will respond to most of the treatments listed above, but dermatologists may also utilize ultraviolet light therapy or cyclosporine in addition to topical therapies. Such treatments have minimal or no effect on arthritis.

Ankylosing Spondylitis

Ankylosing spondylitis (AS) is characterized by inflammatory lower-back pain centering on the sacroiliac joints. Symptoms suggesting sacroiliitis (rather than another cause of back pain) include prolonged morning stiffness and improvement with exercise. Over decades, the sacroiliac joints and spinal vertebrae may fuse, eventually leading to an exaggerated thoracic kyphosis and forward thrusting of the neck.

The extra-axial manifestations of spondyloarthritis can also be present, particularly peripheral arthritis and uveitis.

Characteristics of Inflammatory Back Pain

(Source: Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med 2016.)

Diagnosis

It is common for many years to pass before a diagnosis of AS is made. Usually radiograph or MRI evidence of ankylosing spondylitis is needed to confirm diagnosis.

Testing for HLA-B27 does not usually aid in the diagnostic workup, though the HLA-B27 gene is often present in patients with AS; it is also common in the general population (8% to 10% of white patients).

A trial of NSAIDs can greatly aid in the diagnostic workup, as AS tends to improve substantially with the use of NSAIDs compared to other analgesics.

Nonradiographic Axial Spondyloarthritis

NrAxSpA can be thought of as a preradiographic stage of AS. In some patients, there are unequivocal manifestations of spondyloarthritis with inflammatory back pain, but plain radiographs do not demonstrate sacroiliitis. In such cases, MRI can help identify bone-marrow edema near the sacroiliac joints, suggesting inflammation.

Such patients are diagnosed with nrAxSpa and are treated in a similar manner to AS, with NSAIDs, physical activity, stretching, DMARDs, and bDMARDs.

Diagnostic Algorithm for Axial Spondyloarthritis

(Source: Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med 2016.)

Treatment

• NSAIDs are the main pharmacologic therapy for AS, providing at least significant symptomatic improvement.

• Stretching and physical activity are the main nonpharmacologic treatments for AS. In addition to providing analgesia, stretching in particular will help maintain flexibility of the spine for as long as possible.

• Biologic DMARDs — TNF-alpha inhibitors are highly effective, particularly when there is impairment of daily function despite the combination of NSAIDs, physical activity, and stretching.

• DMARDs — Methotrexate or sulfasalazine might be effective in the setting of peripheral arthritis; they do not provide any substantial benefit in the management of inflammatory back pain.

Inflammatory Bowel Disease (IBD)-Related Arthritis

Diagnosis

IBD-related arthritis is diagnosed when the features of spondyloarthritis are associated with IBD. Features of IBD include hematochezia, diarrhea, abdominal pain, and recurrent aphthous ulcers; confirmation with upper/lower endoscopy and tissue biopsy is usually required, along with specialist assessment by a gastroenterologist. (For more information on IBD, see Inflammatory Bowel Disease in the Gastroenterology rotation guide.)

Peripheral, axial, and extra-articular manifestations of spondyloarthritis might be present. Some patients with IBD-related arthritis will have symptoms that coincide with an increase in IBD activity. In these cases, controlling the IBD will lead to improvements in the arthritis. For the rest, the spondyloarthritis features may persist independently of the IBD activity.

Treatment

• Optimize control of IBD; this may include biologic treatments (such as TNF-alpha inhibitors) that may be particularly effective for inflammatory arthritis or spondylitis.

• Consider NSAIDs, though they may worsen IBD activity and/or increase bleeding risk.

• For peripheral arthritis, consider DMARDs such as methotrexate or sulfasalazine.

• For oligoarthritis, targeted intra-articular steroid injections can be beneficial.

• For uveitis, treatment of acute flares is necessary. If uveitis is recurrent, TNF inhibitors may be appropriate.

Reactive Arthritis

Reactive arthritis is characterized by oligoarthritis occurring with uveitis, conjunctivitis, or urethritis.

In most cases there is a recent (within 3 months) history of a gastrointestinal or genitourinary infection. Typical spondyloarthritis features can be seen, particularly an asymmetric oligoarthritis. Sacroiliitis can occur but is usually asymmetric (in contrast to the symmetrical inflammation of AS).

The prognosis is good, with resolution expected within 3 to 6 months. On occasion the arthritis persists for longer than 12 months.

Diagnosis

The diagnosis is confirmed by identifying a causative microorganism from stool samples (such as Salmonella species) or urine samples (especially Chlamydia trachomatis), in conjunction with a compatible disease presentation of spondyloarthritis.

Causative organisms include:

• Chlamydia spp. (especially C. trachomatis)

• Campylobacter jejuni

• Yersinia enterocolitica

• Shigella spp. (especially S. flexeneri)

• Salmonella spp.

Treatment

In mild cases, NSAIDs may suffice until the features resolve. In more severe cases, glucocorticoids are required (either intra-articular or systemic) as well as DMARDs. Sulfasalazine is often used in the first instance, or weekly oral methotrexate, though their efficacy is variable.

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