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7 Articles in this Series
Introduction
Addressing Arthralgia in Children
An ACR/ARHP Preview
Axial Spondylitis: Mimics, Progression, the Need for MRI, and New Management Recommendations
How Rheumatic Diseases Can Hurt Sexual Health
Tanezumab for Hip and Knee OA; Cosentyx for Ankylosing Spondylitis; and Upadacitinib for RA
Treating Chronic Musculoskeletal Pain in Older Adults
Uncovered Inflammatory Pathways of Osteoarthritis Call for New Targets

Axial Spondylitis: Mimics, Progression, the Need for MRI, and New Management Recommendations

Shared cases differentiate axSpA from similar conditions, reveal disease progression, and provide evidence for emerging treatment protocols. An ACR/ARHP 2018 annual meeting highlight with Lianne Gensler, MD, Atul Deodhar, MD, and Michael Ward, MD

 

Ankylosing Spondylitis (AS) and Non-Radiographic Axial Spondyloarthritis (Axial SpA, or axSpA) were addressed in several 2018 ACR/ARHP annual meeting sessions. One presentation, in particular, focused on how to differentiate axSpA from similar conditions, or mimics, progression of the disease, and emerging treatment protocols, including a pending update to the ACR/SAA/SPARTAN recommendations. SAA is the Spondylitis Association of American, and SPARTAN is the Spondyloarthritis Research and Treatment Network.

Spondylitis xray Spondylitis xray - MRI scans may help to further confirm diagnosis. (Source:123RF)

Identifying axSpA Mimics

Launching the presentation was Lianne Gensler, MD, an associate professor of medicine in the Division of Rheumatology at the University of California, San Francisco (UCSF) and the San Francisco Veteran Affairs Medical Center. She is the director of the Spondyloarthritis clinic and research program at UCSF. She shared four case studies that appeared to be probable or likely axSpA, but that ultimately turned out to be something else.

The following four mini case examples were based on her caseload; each one utilized both T1 and STIR MRI sequences to aid in diagnosis.

  • Case 1: A 30-year-old female experienced inflammatory back pain (IBP) after delivering her first child and had pain on her left side/low back region. She had classic IBP, and a history of JIA and anterior uveitis. Exercise did not help. She found some relief with NSAIDS. Her physical exam was unremarkable. She had a low (1.4) axSpA disease activity score. An Anterior-Posterior Pelvis radiograph suggested inflammatory arthropathy. Asked Dr. Gensler, was an MRI needed based on this history and exam, or could she make a diagnosis? She chose MRI to confirm any inflammatory burden and structural damage.

The mimic: As it turned out, the patient had experienced a postpartum sacral fracture. This axSpA mimic was identified only by MRI.

  • Case 2:  A 31-year-old male reported five years of low back pain with the pain recently worsening in the morning/evening and while running. NSAIDs helped a little. Recently, he had lost weight, experienced diarrhea, and had knee pain. He reported a history of Crohn’s Disease, past TNFi use (lost response), and past peripheral Type I Arthritis. Upon exam, there was no eye inflammation or rash, and was overall unremarkable. His gastrointestinal doctor had prescribed another TNFi two weeks prior for his IBD and back pain. Noted Dr. Gensler, “A physical exam may not always reveal MSK abnormalities, especially in early disease states of axSpA.” This patient’s inflammatory markers were elevated and he had a high disease activity categorization. X-rays showed nothing abnormal.

The mimic: An MRI of the pelvis / sacrum, however, showed bright signal in the sacrum – identifying sacral bone marrow edema. An axial view, which is not usually used for sacroiliitis identification, revealed edema around the rectum and a fistula to the presacral area. His Crohn’s Disease had led to osteomyelitis. (See also an ACR 2018 annual meeting release on how bone marrow edema location may help distinguish axSpA from similar conditions at www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/958.)

  • Case 3: This 32-year-old patient had a diagnosis of axSpA and presented with classic inflammatory symptoms. He was responsive to NSAIDs but had an unclear response to TNFi. An unremarkable exam coupled with a 2.1 high disease activity categorization led Dr. Gensler to order an X-ray of the AP Pelvis, which highlighted the left sacroiliac joint suggesting psoriatic arthritis/sacroiliitis. MRI of the pelvis /sacrum showed no structural change, no fat around the SI joint, no subchondral fat. The local radiologist suggested there were erosions.

The mimic: Unsure of this possibility, Dr. Gensler reviewed the images again with an expert radiology colleague and they realized there was asymmetry of the pelvis, suggesting possible abnormal loading. Bone marrow edema was present, likely from biomechanical stress. The erosions were actually cysts and the radiographer’s structural change report was inaccurate. “It’s important to provide clinical context to a radiologist,” she said. These complicated diagnoses are “not simply a biopsy report.”

  • Case 4: Dr. Gensler’s fourth and final mimic example initially seemed to point to a diagnosis of significant anemia related axSpA. The patient, however, ended up having Acute Lymphoblastic Leukemia with bone marrow infiltration and infarcts. “This case served as a reminder that MSK and bone pain complaints can be manifestations of hematologic malignancies, especially in children,” she said. This patient was 19 and reported worsening MSK/bone pain, without NSAID relief, six weeks after a full workup, including a normal MRI scan. “We would not have found the leukemia if we had not done a repeat MRI and the astute radiologist suggested a differential diagnosis including a marrow infiltrating neoplasm,” she said.

 

Questions Surrounding axSpA Disease Progression and When to Start Treatment

In the second part of the presentation, Atul Deodhar, MD, professor of medicine and medical director of the Rheumatology Clinics at Oregon Health & Science University, in Portland, addressed disease modification. He also served as a core member of the ACR/SAA/SPARTAN treatment recommendation update team (see details below).

Dr. Deodhar kicked off his discussion by asking the audience whether radiographic progression of axSpA can be inhibited. Preventing erosions, osteoporosis, new bone formation (osteoproliferation), and ankylosis are all key, he said, but so are the long-term complications of AS. “Shouldn’t we aspire for ‘disease modification’ to mean change in the natural history of the disease, rather than just prevention of radiographic progression?” he proposed. “And, at what stage should we aspire to make this change? We are 10 to 15 years behind prevention of this disease compared to prevention of rheumatoid arthritis.”

He reviewed with the audience the three pathways to osteoprolieferation:

  • bone morphogenic protein signaling
  • WNT signaling
  • hedgehog signaling.

All these pathways lead to osteoblast differentiation (see Lories R, Rheum Dis Clin NA, 2012), he said, and “studying these pathways are important to finding molecular targets for treatment.”

Editor’s Note: Dr. Deodhar also shared Schett et al, Nature Review Rheum, 2017, for clinicians who wish to better understand mesenchymal proliferation and new bone formation triggers, which, in axSpA, occur at the entheseal sites. See also an ACR 2018 annual meeting press release on how genetic risk scoring may help identify AS earlier at www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/957.

How can structural progression be better assessed? 

We know the axSpA risk factors, said Dr. Deodhar. For example: male, smoking, high CRP, mSASSS baseline, MRI positivity for fatty lesions and BME, heavy physical activity, and HLA-B27+. And today, mSASSS scores are typically used for assessment, but he stated, a recent literature review showed that these scores moved only one unit forward over two years (see van der Heijde et al, Rheum [Oxford], 2018). MRI, in turn, has offered a major advance in understanding the progression of this disease, as demonstrated by Dr. Gensler above and included in the updated ACR/SAA/SPARTAN recommendations below. But the real new kid on the block, he said, is the low-dose CT Scan and the new scoring system being developed, he said. Called the CT syndesmophyte, this tool is currently being validated (see de Bruin et al, Ann Rheum Dis, 2018).

“We will see this more in clinical trials as progression via X-rays show change too slowly,” he said. “Then, any structural damage can be compared to the MRI scans.”

Are the current theories enough?

Referring to the pending ACR/SAA/SPARTAN recommendations for treating AS and axSpA, Dr. Deodhar said the team looked at NSAIDs, PT, TNFi, SEC, and alternative therapies as part of their review. He discussed how some questions have been raised, leading to a few changes in the updated recommendations.  Below is an overview of the questions raised to date, according to his presentation:

  • Is exercise a useful regiment for axSpA? “Exercise has become somewhat controversial in this disease treatment,” he noted. Further, “smoking and job type have shown to have indirect not direct influences on structural progression as measured by mSASSS.”
  • Is new bone formation driven by mechanical strain? Dr. Deodhar referred to a study by Jacques, Ann Rheum Dis, 2014 – what he called the hanging-by-their-tail mice trial. Based on that trial’s results, mechanical stress may have a role in disease progression as does inflammation, which ultimately leads to new bone formation, he said.
  • When should TNFi be implemented into a treatment plan? TNFi users on Celecoxib had less mSASSS progression at 2 and 4 years (see Gensler L, EULAR, 2018). Early use of TNFi was shown to reduce the rate of radiographic progression with a 50% reduction in new bone formation (see Haroon et al, Arthritis Rheum, 2013) while prolonged treatment with TNFi may decelerate spinal radiograph progression in AS (see Maas et al, Arthitis Care Res (Hoboken), 2017). TNF does seem to suppress mesenchemyal proliferation. Other examples are available on his slide deck.
  • The jury is still out for NSAIDs’ role in osteoproliferation. NSAID and diclofenac use seemed to make no difference if taken continuously, or as needed, according to some past research, he noted.
  • Is secukinumab a better option?Secukinumab in AS mSASSS progression at year 4 proved successful.
  • What are the effects of the IL-23/IL-17 pathway on bone in spondyloarthritis? Dr. Deodhar encouraged clinicians to review this new paper (Gravallese E, Nat Rev Rheumatol, 2018), noting that IL-23/IL-17 may lead to bone loss and osteoporosis via osteoclastogenesis. However, he noted, on local periosteal bone, IL23/IL17 might change, leading to local entheseophyte formation. This may then lead to the unique bone phenotype of the co-existence of systemic osteoporosis and periosteal plus etheseal bone formation.

Overall, Dr. Deodhar offered a few conclusions that point to the reasons behind the updated ACR/SAA/SPARTAN treatment recommendations:

  • Progress in osteoimmunology and new imaging modalities has taught clinicians a lot about the pathology and progress of osteoproliferation in axSpA
  • Newer studies will use MRI and low-dose CT for assessment of osteoproliferation
  • Patients with AS should avoid smoking and excessive physical activity
  • Continued use of NSAIDs to prevent osteoproliferation is questionable
  • Whether TNFi and IL-17Ai may reduce signs and symptoms of axSpA and their effect on osteoproliferation needs to be clarified in future studies.

What to Expect with the  Pending AS/axSpA Treatment Recommendations

The NIH’s Michael Ward, MD, MPH, shared additional insight into the pending ACR/SAA/SPARTAN Treatment Recommendations for AS and for axSpA. These  evidence-based draft recommendations are based on the previous GRADE guidelines and on the 2015 consensus recommendations.

The draft update, which is pending board approval, will include new treatment options for consideration depending on the patient’s specific disease activity:

  • Secukinumab
  • TNFi biosimilars
  • Tofacitinib.

The update includes a discussion of how these new options may impact the use of established treatments, such as NSAIDs, spine radiographs and sacroiliac MRI, sulfasalazine, methotrexate and other oral small molecules, and treat to target strategy, with recommendations on when to use each.

The role of imaging in patient management is also addressed. For example, the update promotes the use of a spinal or pelvic MRI to assess activity in adults with AS of unclear activity while on a biologic, but urges avoiding repeat spine radiographs as a standard approach in adults with active or stable AS on any treatment.

Overall, the update aims to provide for successful patient outcomes ranging from health status (highlighting pain and fatigue) to functional status (highlighting physical functioning). The status of the update can be followed at: www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Axial-Spondyloarthritis.

 

 

 

 

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