Spondyloarthritis

The term “spondyloarthritis” (SpA) refers to a group of related and often overlapping disorders, including axial spondyloarthritis, psoriatic arthritis, inflammatory bowel disease (IBD)-related arthritis, and reactive arthritis. These conditions share the following characteristic musculoskeletal manifestations:

• Axial SpA (axSpA, inflammation of the spine and pelvis) can be further subcategorized as follows:

  • radiographic axSpA (also known as ankylosing spondylitis), defined by the presence of x-ray changes consistent with sacroiliitis

  • nonradiographic axSpA, defined by features of axSpA in the absence of changes on x-ray consistent with sacroiliitis

• Peripheral SpA is characterized by the following:

  • peripheral inflammatory arthritis (often an asymmetric oligoarthritis favoring large joints, although small-joint polyarthritis can occur as well)

  • enthesitis (inflammation of tendon insertion points)

  • tenosynovitis (inflammation of the tendon sheath)

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

SpA is also frequently associated with specific nonmusculoskeletal autoimmune manifestations that include the following:

• inflammatory eye disease (particularly acute anterior uveitis)

• inflammatory bowel disease (IBD)

• psoriasis

Clinical Syndromes

SpA is often categorized according to the following clinical syndromes, although it is important to recognize that they frequently overlap:

• psoriatic arthritis (PsA)

• axial spondyloarthritis (axSpA)

• inflammatory bowel disease (IBD)-related arthritis

• reactive arthritis (ReA)

• undifferentiated SpA

  • Patients with features of peripheral SpA without features specifically suggesting PsA, IBD-associated arthritis, or ReA may be classified as having isolated peripheral SpA, occasionally referred to as “undifferentiated” SpA. Some patients with this phenotype may develop axSpA, psoriasis, or IBD later in the disease course.

(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 one or a combination of the following features:

• asymmetric oligoarthritis of large joints (particularly favoring the ankles and knees)

• symmetric polyarthritis of small joints (mimicking rheumatoid arthritis)

• distal interphalangeal joint arthritis (typically seen with nail psoriasis, often mimicking osteoarthritis)

• axial spondyloarthritis (axSpA)

• enthesitis

• 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)

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

Psoriasis: Cutaneous psoriasis (PsO) is present in nearly all patients with PsA, although a minority of patients may develop musculoskeletal manifestations of PsA prior to the onset of cutaneous PsO. The most common form of PsO, plaque psoriasis, is characterized by salmon-colored plaques with overlying silvery scale favoring extensor surfaces such as the elbows and knees. PsO in the context of PsA may be subtle; patients commonly have only small plaques on extensor surfaces or involvement of locations that may not be recognized by patients themselves, including the scalp, intergluteal cleft, or umbilicus. Other forms of psoriasis that can occur in the context of PsA include pustular psoriasis, inverse psoriasis, guttate psoriasis, and erythrodermic psoriasis.

Nail psoriasis is frequently present in patients with PsA and is one of the manifestations of PsO that confer a higher risk of developing PsA. Nail psoriasis may present as nail pitting, fragility, onycholysis, or discoloration.

Diagnosis: PsA is diagnosed clinically with supporting information from investigations. The common features of peripheral 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-cyclic citrullinated peptide (anti-CCP) antibodies; the detection of these antibodies in peripheral blood—particularly at high titers—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.

Imaging: 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, appearing 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

• enthesopathy, 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, often appearing similar to ankylosing spondylitis, though asymmetric sacroiliitis is often seen

As is the case with other inflammatory arthritides, radiographs have a limited sensitivity in detecting PsA. Therefore, the diagnosis should not be ruled out based on normal radiographs if history and physical are otherwise suggestive of the diagnosis.

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

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

• Moderate-to-severe disease: Disease-modifying antirheumatic drugs (DMARDs) are often required.

  • Conventional synthetic (cs)DMARDs (e.g., methotrexate, sulfasalazine, leflunomide) are often effective in peripheral arthritis associated with PsA, although the efficacy of methotrexate may be somewhat more limited in PsA as compared with RA.

  • In some cases of mild-to-moderate disease, apremilast (a phosphodiesterase type 4 inhibitor) may also be used.

  • Recent guidelines for the treatment of psoriatic arthritis recommend initiating on a tumor necrosis factor (TNF) inhibitor (etanercept, adalimumab, golimumab, infliximab, certolizumab pegol) in all patients with moderate-to-severe PsA. This may be especially important for people with axial involvement, as (cs)DMARDs may be ineffective for axial disease.

  • Other medications, such as interleukin-17 (secukinumab, ixekizumab), interleukin-12/23 (ustekinumab), interleukin-23 (guselkumab, risankizumab), or T-cell costimulation (abatacept). Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) are sometimes used as well, although not all of them are approved by the FDA for this indication.

Glucocorticoids may be effective at treating inflammatory arthritis at all stages but tend to be reserved due to glucocorticoid-related toxicities and because cessation of glucocorticoids can trigger a severe flare of psoriasis. When pustular psoriasis or erythroderma are 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 or topical therapies. Such treatments have minimal or no effect on arthritis.

Axial Spondyloarthritis

Axial spondyloarthritis (axSpA) is characterized by inflammatory back pain, often centering around the sacroiliac joints. Symptoms suggesting inflammatory back pain (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, enthesitis, and uveitis.

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

Diagnosis: It is common for many years to pass before a diagnosis of axSpA is made. The diagnosis primarily requires identification of inflammatory back pain. Differentiating between radiographic axSpA (also known as ankylosing spondylitis) and nonradiographic axSpA depends on the presence or absence of sacroiliitis on plain radiographs of the pelvis. Radiographic features of sacroiliitis include sclerosis, joint widening, erosions, and ankylosis. Radiographs of the cervical, thoracic, and/or lumbar spine can be obtained when patients have symptoms localized to those regions, as characteristic findings of anterior bridging syndesmophytes can support the diagnosis.

Testing for HLA-B27 does not usually aid significantly in the diagnostic workup of axSpA. Although the gene is often present in patients with axSpA, it is also common in the general population (8% to 10% of patients of European ancestry).

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

Nonradiographic axial spondyloarthritis: It is unclear if nonradiographic axSpA is a preradiographic stage of radiographic axSpA or a distinct entity. In patients with nonradiographic axSpA, there is evidence 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. Rarely, MRI can fail to detect inflammatory lesions despite a strong clinical suspicion for spondyloarthritis, in which case response to treatment of axSpA may help identify the diagnosis.

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

Treatment: Patients with radiographic and nonradiographic axSpA are treated in a similar manner with NSAIDs, physical activity, stretching, and DMARDs.

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

• Stretching and physical activity are critical elements of the nonpharmacologic management of axSpAS. In addition to providing analgesia, stretching in particular helps maintain range of motion of the spine.

• (cs)DMARDs such as methotrexate do not provide substantial benefit in axial involvement.

• Treatment with biologic DMARDs is indicated when symptoms persist despite NSAIDs and physical therapy. TNF inhibitors are highly effective, particularly when impairment of daily function persists despite the combination of NSAIDs, physical activity, and stretching. Other therapeutic options include interleukin (IL)-17 inhibitors and JAK inhibitors.

Inflammatory Bowel Disease (IBD)-Associated Arthritis

Diagnosis: IBD-associated 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 SpA might be present. Some patients with IBD-associated arthritis have joint symptoms that coincide with an increase in IBD activity, especially in patients with peripheral SpA manifestations. In these cases, controlling the IBD will lead to improvements in arthritis. For the remaining patients, SpA features may persist independently of 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 axial SpA.

• NSAIDs are often best avoided, as they may worsen IBD activity, increase bleeding risk, or both; however, if felt to be safe from a gastrointestinal perspective, these can be considered for musculoskeletal manifestations.

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

• For oligoarthritis, targeted intra-articular glucocorticoid 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 (ReA) is most often characterized by oligoarthritis occurring with uveitis, conjunctivitis, or urethritis. Most patients have a recent (within 3 months) history of bacterial infection. Many infections have the potential to lead to ReA, but gastrointestinal and genitourinary infections are the most common causative agents. Patients with ReA may have typical SpA features, particularly an asymmetric oligoarthritis of the lower extremities. If sacroiliitis occurs, it is usually asymmetric (in contrast to the symmetrical inflammation of axSpA).

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.

Typical causative organisms include:

• Chlamydia spp. (especially C. trachomatis)

• Campylobacter jejuni

• Yersinia enterocolitica

• Shigella spp. (especially S. flexneri)

• Salmonella spp.

Treatment: In mild cases, NSAIDs often suffice until the features resolve. In more-severe cases, glucocorticoids may be required (either intra-articular or systemic) as well as DMARDs such as sulfasalazine or methotrexate.

Patients with ReA have a good prognosis, with resolution expected within 3 to 6 months. On occasion, the arthritis persists for longer than 12 months, especially in patients with the HLA-B27 gene.