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16 Articles in Volume 20, Issue #5
20/20 with Drs. Carmen R. Green and Johnathan Goree: Racial Disparities in Pain Care
A Kratom Primer: Miracle Medicine or Herb of Abuse?
A Pilot Study: Incidence and Prediction of Diversion among Opioid Therapy Patients
Analgesics of the Future: G-Protein Biased Mu-Opioid Receptor Ligands
Application Note: Decellularized Human Placenta in the Treatment of Infracalcaneal Heel Pain
Are Clinicians Effectively Counseling Patients on Safe Opioid Storage and Disposal? Survey Results
Ask the PharmD: How to Manage Pain Meds During Pregnancy?
Behavioral Medicine: Managing Anxiety and Maladaptive Behaviors
Case Report: Spinal Cord Stimulation for the Treatment of Pain Associated with Chronic Pancreatitis
Differential Diagnoses: Inflammatory or Non-inflammatory Chronic Back Pain?
Pelvic Inflammatory Disease: Diagnosis, Education, and Treatment Options
Product Review: Non-Invasive Neuromodulation for the Treatment of the Most Difficult Pain Conditions
Provider Perspective: Carpal Tunnel's Association with Hypothyroidism
Research Insights: Opioid Use During the Peripartum Period – What to Expect
Special Report: Race, Pain Management, and the System
When Patients Become Pregnant: How to Maintain Chronic Pain Management

Differential Diagnoses: Inflammatory or Non-inflammatory Chronic Back Pain?

Two cases illustrate differences in symptoms and treatment approaches. Plus, a look at the axial spondyloarthropathies associated with inflammatory back pain: ankylosing spondylitis, psoriatic arthritis, reactive arthritis, IBD-associated arthritis.

Chronic back pain can be broadly categorized as inflammatory or non-inflammatory. This article will use two hypothetical patient cases to focus on the clinical features that best distinguish inflammatory from non-inflammatory back pain and review each patient’s evaluation and management. The various types of inflammatory back pain, often lumped together as axial spondyloarthropathies, as well as their therapies, will also be discussed

 

Case Presentations

Case 1

A 43-year-old man reports having low back pain for the past 8 months. He works at a desk most of the day and finds that he needs to get up frequently and move about or else he feels his back “tightening up.” There has been no obvious trauma and his general health is good, other than an elevated blood pressure, which is currently being treated with a diuretic. For the past 6 months, the back pain is bothering his sleep and is better when he starts moving around after breakfast. He walks every day at noon for about 45 minutes and reports generally feeling better as he walks but then his back “stiffens an hour later when he is back at work.” In the past few months, he has also noted neck pain and stiffness. He has been taking OTC ibuprofen, usually 2 at a time, and gets some pain relief from that. Currently, the pain is described as dull, but persistent, and involves the neck, mid and lower back, and buttocks.

There is no radiating pain and no neurologic symptoms to suggest sciatica nor any systemic complaints. A recent back and pelvis X-ray demonstrated no abnormalities. The general physical examination is unremarkable. Joint examination reveals no joint swelling or inflammation. Back examination demonstrates no spinal tenderness but moderate pain when moving his neck and lower back through a range of motion. The strength is good and there are no neurologic abnormalities.

Case 2

A 48-year-old man presents with a history of low back pain for the past 10 months. His pain is aggravated by any activity, especially when he reaches down or tries to stretch. He feels better when he lies down flat but his pain gets progressively more severe during the day. He recalls having similar symptoms 20 years ago following a long hike, but the symptoms went away in a few weeks. Ever since then, he states that, “My back can go out for a few days.”

During the past 6 months, he has been unable to continue his regular tennis and golf routine because the activity aggravates his back pain.

He experiences “minimal pain relief” after taking two or three OTC ibuprofen or acetaminophen pills. His general health is good, and he is taking no medication routinely. There are no neurologic or systemic symptoms.

The physical examination was normal. Back examination revealed no focal tenderness with pain on full motion of the lumbar spine. There were no neurologic abnormalities and the strength was good. An X-ray of the pelvis and lumbar spine was unremarkable.

 

Differential Diagnosis

At first glance, these two patients appear to have very similar symptoms and a nearly identical, quite unremarkable physical examination. Both patients are quite young and in good general health. Their spinal X-rays revealed no obvious abnormalities, essentially excluding any major structural abnormalities. Since their symptoms have lasted more than 6 months, the likelihood of any dangerous medical condition, such as an infection or cancer, is extremely low.

Twenty percent of the population experiences chronic low back pain, defined as lasting more than 3 months and present on most days.1,2 In some studies, as many as one-quarter of individuals with chronic low back pain will have an inflammatory cause for that pain3 although in most prospective studies of patients with chronic low back pain, only about 5% are formally diagnosed with an inflammatory back disease.4

Symptoms that suggest inflammatory back pain include:3,4

  • Insidious onset
  • Morning stiffness > 30 minutes
  • Pain lessens with activity or exercise
  • Pain wakens during the second half of night
  • Buttock pain

Hart and colleagues were the first to accurately describe symptoms of inflammatory back pain in 1949: “A frequent feature of the pain and stiffness was the aggravation caused by

immobility. Waking in the morning stiff and in pain, the patient gradually became more supple during the day, feeling at his best from the afternoon until bedtime. One patient noted that with frequent exercise, his condition was kept in check, but confinement to bed for any cause made him worse. Another woke himself up every 2 hours throughout the night to exercise his spine as otherwise, he suffered unduly in the morning.”5 

 

Return to Case 1

The first patient’s symptoms of morning stiffness, pain made better with exercise, and buttock pain suggest inflammatory back pain. The difficulty with movement in his neck as well as the lower back suggests possible involvement of the cervical spine. It would be important to ask this patient about any chest wall discomfort and look for limited chest expansion. The distribution of signs and symptoms in patients with inflammatory back pain often include the cervical and lumbar spine, chest wall and buttocks (note that these areas may also be affected with non-inflammatory pain). See Figure 1.

Figure 1 based on the NHANES IBP/SpA instrument for identifying history of chronic pain, aching or stiffness at one of several specific axial locations (see Reference 3 Weisman).

Preliminary laboratory tests would include acute phase reactants, either an ESR or a CRP, which should be elevated. An HLA-B27 genetic test may be ordered, especially if there is a family history consistent with inflammatory back disease.

In light of the first patient’s symptoms, referral to a rheumatologist or physical medicine and rehabilitation (PM&R) specialist at this time would be advisable. Musculoskeletal specialists have more experience with the examination of the sacroiliac (SI) joint, documenting restricted spinal movement and in the evaluation of limited chest expansion, both signs of inflammatory back pain. Often, subtle spinal or SI abnormalities are missed and the specialist would review the X-rays and obtain cervical spine X-rays. If the X-rays are all normal, imaging studies (MRI) of the sacroiliac joints should be obtained.

Since there is no indication of a systemic disease such as psoriasis or inflammatory bowel disease (IBD), it is most likely that this patient has an early stage of AS (see below for detail on AS and other inflammatory back diseases.) This diagnosis could be confirmed by evidence of sacroiliitis on imaging studies by the specialist. A significant number of patients with AS have normal radiographs of the SI joints or spine, especially early in the disease, but have abnormal findings on MRI. The earliest inflammatory changes can include bone marrow edema of the subchondral or periarticular SI areas. MRI of the spine should be obtained in Patient 1 as the imaging is more sensitive than X-rays in picking up early lesions in the lumbar and cervical vertebrae.

This patient’s initial management may include a trial with more potent, long-acting NSAIDs and referral to physical therapy under a PM&R clinician’s guidance. A rheumatologist may choose to immediately begin a disease-modifying medication, including one of the biologic drugs discussed below.

 

Return to Case 2

Patient 2 has symptoms much more consistent with non-inflammatory back pain. These include:

  • Pain that worsens with activity, exercise
  • Pain that is relieved by lying down
  • No prominent morning stiffness
  • Pain that often comes and goes but may suddenly worsen for brief periods
  • No buttock pain or tenderness

In contrast to Patient 1, Patient 2 requires no further X-rays or imaging studies and instead should be treated primarily with non-pharmacologic multidisciplinary management. Routine laboratory tests, including a complete blood count and acute phase reactants, may be reasonable (the acute phase reactants should be normal). A PM&R and pain specialist could be consulted if the patient’s symptoms do not improve with conservative management.

Editor’s Note: See PPM’s recent roundtable and review on approaching low back pain from different clinical specialties: 

 

Axial Spondyloarthropathies (axSpA) and the Connection to Inflammatory Back Pain

Axial spondyloarthropathies (axSpA), sometimes called axial spondyloarthritis, are a group of inflammatory diseases affecting the spine and sacroiliac joints. Shared features include:

  • Anatomic regions primarily affected are the spine and sacroiliac joints
  • Rheumatoid factor is negative
  • Strong association with HLA-B27
  • Often involve peripheral joints, ligaments, tendons
  • These conditions may be associated with dermatologic and systemic diseases

Historically, axSpA were often referred to as seronegative spondyloarthropathies, since they are rheumatoid factor (ie, serologically) negative. AxSpA are more common in men and have a genetic predisposition. The prototype is AS, but axial spondyloarthropathies also include psoriatic arthritis, reactive arthritis, and inflammatory arthritis associated with IBD – each reviewed below.

 

Ankylosing Spondylitis

Ankylosing spondylitis is not associated with any other systemic disease. The spinal disease in AS tends to be more widespread and severe than in other types of axSpA and the peripheral joint arthritis less prominent. Among the axSpA, AS has the strongest association with the gene for the human leukocyte antigen (HLA)-B27 and therefore has a strong familial predisposition. More than 90% of AS patients are HLA-B27 positive.6 About 50% to 60% of patients with the other forms of axSpA are positive for the HLA-B27 antigen. The prevalence of axSpA in the United States is 1.4% and of AS is 0.6%.6 Since HLA-B27 is a genetic trait, its prevalence, and that of axSpA, varies with ethnicity and nationality. The presence of HLA-B27 in the general population in different countries varies from 5% to 10%.6

The diagnosis of an axSpA inflammatory back disease can be confirmed with radiologic or imaging studies. Plain anterior-posterior (AP) X-rays of the SI joints, pelvis, and lumbar spine films may be ordered initially, but if there is no evidence of sacroiliitis or lumbar vertebral abnormalities, an MRI of the SI joints should be obtained. The standard view of the pelvis includes the hip joints, which can be involved in early AS. Although plain X-rays and imaging studies in patients with axSpA may be unremarkable for a number of months, the diagnosis is considered tentative unless such X-ray or imaging abnormalities are present. Repeat imaging may be considered at 3 and/or 6 month follow-up. (Note that imaging recommendations for axSpA were recently updated by the American College of Rheumatology (ACR), Spondylitis Association of America (SAA), and the Spondyloarthritis Research and Treatment Network (SPARTAN).

 

There are a number of extra-articular abnormalities that may be present in patients with AS. Non-spinal AS features may include:

  • Asymmetric arthritis of a few lower extremity joints (oligoarthritis)
  • Heel pain (enthesitis)
  • Anterior uveitis
  • Insidious hip and shoulder arthritis

Each of these findings may also prominent be in the other forms of axSpA discussed below. An inflammatory, asymmetric oligoarthritis, involving just one or two joints, is common. In contrast to rheumatoid arthritis, this is never a bilateral, symmetric polyarthritis of the hands and feet. Inflammation of the insertion of the Achilles tendon and plantar fasci into the calcaneus, termed an enthesitis, may cause heel pain and local tenderness. Iritis or anterior uveitis may cause eye pain, redness, and visual disturbances. Acute anterior uveitis may be the initial manifestation of AS or another axSpA, and 50% of patients with uveitis will be diagnosed eventually to have an axSpA.7 There is a strong association of the HLA-B27 antigen with uveitis, even in patients with no evidence for an axSpA.7

Physical examination for AS should include a careful evaluation for restricted motion of the cervical, thoracic, and lumbar spine. Patients with advanced AS tend to present with forward stooping of the cervical and thoracic spine – the “hunchback” posture. A simple test is to ask the patient to stand erect, with the back against a wall, keeping the chin horizontal. Normally, the individual should be able to touch the occiput against the wall. Chest expansion is measured at the fourth intercostal level and normal expansion is > 2 cm. There are a number of techniques to measure forward flexion of the lumbar spine. Hip range of motion should be carefully evaluated as well since the insidious onset of hip arthritis may mask progressive joint damage.

In any patient under the age of 45 with chronic low back pain and non-spinal features (as laid out above) a diagnosis of AS can be made with a high degree of certainty, and a positive HLA-B27 test would be strong confirmatory evidence. Nevertheless, many experts would not make a definite diagnosis of AS without X-ray or imaging SI or spinal abnormalities.

Psoriatic Arthritis

Psoriatic arthritis (PsA), like the other forms of axSpA, may have spinal involvement similar to that in AS, but more often also has peripheral joint inflammation. Characteristic features of PsA include:

  • Psoriasis
  • Nail changes
  • DIP joint inflammation
  • SI and/or spinal arthritis (HLA-B27 positive)
  • Dactylitis (sausage digit)
  • Asymmetrical oligoarthritis
  • Negative rheumatoid factor

 

PsA has often been subdivided based on its pattern of arthritis:

  • An axial spondyloarthropathy (axSpA)
  • Distal, small joint polyarthritis, especially involving the distal interphalangeal (DIP) joints
  • An asymmetric, mainly lower extremity, oligoarthritis
  • A symmetric, small joint polyarthritis, very similar to rheumatoid arthritis

However, many patients have more than one of these joint patterns, and, not infrequently, those with axSpA have a concurrent peripheral joint arthritis.

Psoriasis must be present at some point in time for the diagnosis, but the skin manifestations may precede any joint disease for months or even years and occasionally no skin abnormalities are obvious until the arthritis has been well-established. About 80% of patients will have had psoriasis first or around the same time that the arthritis began. Nail and scalp involvement are more common in psoriasis patients who also have arthritis. The prevalence of psoriatic arthritis in patients with psoriasis is around 20% and is slightly higher in those with more extensive skin disease.8 About 40% of the time, the joint involvement in PsA includes the SI joints and spine.9 These patients will usually be HLA-B27 positive. Usually the spinal involvement is less extensive than in AS, but about 25% of patients have findings clinically and radiologically indistinguishable from AS.9 The risk of having an axSpA in a patient with psoriasis is 5 to 7 times greater than in the general population.10

The peripheral joints involved most often are the DIP joints of the hands or feet. When the DIP joints are inflamed, there are often associated nail changes, with pits and onycholysis, pathognomonic for psoriatic arthritis. A whole finger or toe may be swollen and inflamed, referred to as dactylitis or a “sausage digit.” Dactylitis is present in 50% of cases of psoriatic arthritis and very suggestive of that diagnosis when present. X-ray or imaging studies demonstrate evidence of sacroiliitis in one-third of psoriatic arthritis and correlate with the presence of axSpA and a positive HLA-B27 antigen.

Reactive Arthritis

Reactive arthritis, in the past termed Reiter’s syndrome, is an axSpA that follows a presumed infection, although viable microbes are not found in the joint or blood. A number of infectious agents, including Chlamydia trachomatisYersiniaSalmonellaShigella, Campylobacter, Escherichia coliClostridioides difficile,and Chlamydia pneumoniae have been incriminated, primarily based on epidemiologic tracking.11 Most cases develop acutely, 1 to 4 weeks after a suspected or confirmed genitourinary or gastrointestinal (GI) infection. Many patients have either persistent diarrhea or urethritis at the time of diagnosis. A stool or urethral sample will demonstrate a pathogen in 50% of cases diagnosed with a reactive arthritis.11

The most common presenting manifestation is acute oligoarthritis, most often in a knee or ankle. Characteristic features of reactive arthritis are:

  • Preceding gastrointestinal or genitourinary infection
  • Urethritis or diarrhea
  • Acute oligoarthritis
  • Sacroiliitis
  • Heel pain
  • Dactylitis
  • Conjunctivitis
  • Oral lesions
  • Genital lesions
  • HLA-B27 presence

As with the other axSpA, SI joint inflammation, dactylitis, and heel pain related to enthesitis may be present. In contrast to AS, the ocular manifestations are typically conjunctivitis rather than uveitis. Oral lesions such as painless mucosal ulcers, and painless genital lesions, termed circinate balanitis, are unique to reactive arthritis. In contrast to the other forms of axSpA, reactive arthritis is usually self-limited, with complete symptom resolution within 6 months.11

 

Arthritis Associated with Inflammatory Bowel Disease (IBD)

An axSpA and/or a peripheral arthritis are present in 10% to 20% of patients with ulcerative colitis or Crohn’s disease.12 Arthritis associated with IBD may present either as:

  • an AxSpA that is indistinguishable from ankylosing spondylitis and which does not correlate with activity of IBD and HLA-B27 in those patients, or
  • a peripheral oligoarthritis, activity does correlate with IBD symptoms.

Features consistent with AS in IBD vary greatly in different series from 1% to 26%.13 AS may be the only non-GI manifestation of IBD and is more common in males with IBD. Patients with AS should be screened for possible IBD. The peripheral joint arthritis is usually an oligoarthritis, most often in one knee and often remits spontaneously if the IBD is under good control. In contrast, the axSpA does not correlate with the symptoms of IBD. The HLA-B27 may be present in 50% to 75% of patients with IBD and an axSpA.13 Erythema nodosum may be present in those IBD patients who have inflammatory, peripheral arthritis. The peripheral arthritis is seldom deforming.

 

Managing the Spectrum of Axial Spondyloarthropathies

Physical therapy is essential to the optimal management of any patient with persistent axSpA, nearly universal in ankylosing spondylitis but also common in psoriatic arthritis and arthritis associated with IBD. Deformities, such as the dreaded “hunchback” posture, can be largely prevented with careful attention to posture and with specific exercises. Such exercises should include formal deep breathing techniques to improve chest expansion and back mobility exercises. Water exercises and swimming are often more effective than land-based exercise and sports.3

Patients with mild, intermittent peripheral arthritis can be managed with prescribed NSAIDs and supplemented with intraarticular corticosteroid injections, if appropriate. Since reactive arthritis tends to remit spontaneously, medications may only be required for a few months. However, most patients with AS or PsA will have persistent symptoms that correlate with progressive joint damage, deformity, and disability. In these patients, it is important to use disease-modifying drugs (eg, TNF, interleukin or JAK inhibitors) and to begin them before irreversible joint damage ensues. As with rheumatoid arthritis, the treatment of axSpA has been dramatically improved during the past 20 years with potent biologic medications.

A tumor necrosis factor (TNF) inhibitor, such as etanercept, infliximab, or adalimumab, are usually initiated in any axSpA patient with persistent symptoms and evidence of joint damage on X-ray or imaging studies.14 There is no evidence that methotrexate or other disease-modifying drugs offer added benefit, so the biologics are used alone in most situations. Generally, symptom relief is noted quickly, within 2 to 3 months. Interleukin 17 (IL-17) inhibitors and Janus kinase (JAK) inhibitors have also been shown to be effective in treating axSpA, including AS, psoriatic arthritis, and axSpA associated with IBD.14 (See also, PPM’s clinical primer on TNF inhibitors.)

The choice of a biologic or an immunomodulatory medication will vary from case to case with advanced psoriasis or IBD, and the specific drug used is often based on the provider’s specialty and experience with the drug (ie, whether a rheumatologist, dermatologist, or gastroenterologist).

Of note, approximately 20% of patients with axSpA have chronic, widespread pain and meet clinical criteria for fibromyalgia.15 More on fibromyalgia and co-existing chronic pain disorders. These patients have worse disease activity scores and poorer quality of life. It is important to determine whether persistent pain (and fatigue if applicable) are related to the axSpA or concurrent fibromyalgia in order to prevent needless, more aggressive therapy.

 

Conclusion

The majority of individuals with chronic low back pain have non-specific low back pain. Another large group of chronic low back pain patients have structural disorders, such as spinal stenosis. Inflammatory back pain is less common, varying from 5% to 20% in population studies of chronic low back pain. However, it is essential to differentiate inflammatory from non-inflammatory back pain.

Clinicians should suspect inflammatory back pain in younger individuals, especially men under 45 years of age, when the pain lessens with exercise and worsens at rest, and when there is prolonged morning stiffness and buttock pain. An elevated ESR or CRP and the presence of HLA-B27 are strong laboratory evidence for inflammatory back pain, but a definitive diagnosis requires radiologic or imaging confirmation.

Inflammatory back pain diseases include a number of related conditions, classified as axial spondyloarthropathies: ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and arthritis associated with inflammatory bowel disease. Treatment for these conditions is similar and, in patients with progressive axial or peripheral arthritis, biologic and immunomodulatory medications are often very effective.

Last updated on: October 12, 2020
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