A flare can be defined as the acute worsening of symptoms. Flares are generally thought to be due to increased activity of the underlying disease although this cannot always be demonstrated objectively. In rheumatoid arthritis and systemic lupus erythematosus flares are accompanied by joint swelling, rashes, or lab abnormalities. Patients with peripheral spondyloarthritis may similarly develop swollen joints during a flare. On the other hand, the major symptoms of axial inflammation in spondyloarthritis (back pain, stiffness, fatigue) are experienced and cannot be assessed by physical examination. Inflammatory markers in the blood may be normal. This can make it difficult to clearly attribute a temporary worsening of symptoms to increased inflammatory activity. Magnetic resonance imaging (MRI) can demonstrate inflammation in the joints or spine. However, there are issues with access, cost and sensitivity that make it impractical to perform MRI scans on every spondyloarthritis patient with worsening of symptoms.
Studies from the pre-biologic era demonstrated that fluctuations in disease severity are common in ankylosing spondylitis which likely reflects the experience of all patients with spondyloarthritis. According to these studies, a typical AS flare is characterized by increased back pain that may be stabbing in nature or feel like muscle cramps. Symptoms can be local or more generalized. Increased fatigue and emotional upset are common. Episodes may last from a few days to a few weeks. To measure flares in clinical studies, researchers have tried to develop definitions using established disease activity measures. A recent consensus paper from the Assessment in SpondyloArthritis International Society (ASAS) defined a clinically important worsening of axial spondyloarthritis activity (= flare) as an increase in Ankylosing Spondylitis Disease Activity Score (ASDAS) of at least 0.9 points. However, this research definition poorly captures what patients experience. Andrew Keat, a rheumatologist from the UK, put it like this: “a flare is whatever a patient experiences that might broadly be characterized as a worsening in comfort or well-being.”
What causes a flare?
Long-term studies of biologics have demonstrated that improvements in disease activity achieved over the first few weeks to months of therapy are typically stable over time. However, this does not exclude the possibility that individual patients may experience temporary flares while being on a biologic. TNF or IL-17A inhibitors are effective for many patients but they only suppress inflammation, they do not cure the disease. The majority of patients with axial spondyloarthritis whose disease is in remission on a biologic will flare after stopping the drug, an observation that has been confirmed in multiple clinical studies. Some flares are thus easily explained by treatment interruption or discontinuation, delaying doses or extending the time between doses, or by loss of efficacy of the drug. However, flares may also be the results of “random” fluctuations in disease activity regardless of whether someone is being treated with a biologic, other anti-inflammatory medications, or not taking medications. What exactly happens in those situations is not well understood and likely involves multiple factors. In one study, patients linked flares to situations of increased emotional stress or an episode of “overdoing it.” Infections are another potential trigger. The inability to follow established exercise routines during the COVID-19 pandemic has been a recent problem.
Dealing with a flare
Typical flares are limited in time lasting days to weeks and many patients may have found their own ways of dealing with the situation. Such coping strategies may include re-starting NSAIDs or increasing the daily dose, changes in the exercise routine, long hot baths or showers and other nonpharmacological interventions. However, if symptoms are unusual or prolonged seeing the rheumatologist is recommended to find out what is going on. Make note of any patterns if flares happen repeatedly. For instance, if symptoms increase prior to the next dose of the biologic with substantial improvement after the injection, the dose may be too low or neutralizing anti-drug antibodies may have formed that reduce the efficacy of the drug. This may be helped by increasing the dose or by switching to an alternative medication.
Are you sure it’s just a flare?
It is important to realize that a change in symptoms may be unrelated or only indirectly related to spondyloarthritis. A number of conditions need to be distinguished from a flare.
In patients with ankylosing spondylitis and limited range of motion due to spinal fusion, minor trauma can result in a fracture. Biologic therapies also predispose to severe infections, which occasionally may affect the spine. Fractures and spinal infections require immediate medical attention. Example situations include a patient with ankylosing spondylitis who develops severe neck pain after involvement in a rear-end collision, or a patient on a TNF inhibitor with new back pain, malaise, fever and chills.
Spondyloarthritis can also be associated with development of pain sensitization also known as fibromyalgia. The difference from a flare is that the symptoms are not caused by increased inflammatory activity in the spine, SI, or other joints. Rather, it is thought that the pain threshold in the central nervous system is altered. Sensory signals from the back and extremities that are normally innocuous, registering little to no pain, are now perceived as being painful. Distinguishing pain sensitization from a spondyloarthritis flare can be difficult but is important as the management approach is very different.
Spondyloarthritis is associated with inflammation in other organs, namely in the skin (psoriasis), eye (uveitis), and intestine (inflammatory bowel disease). These extra-skeletal manifestations (symptoms that occur in locations other than the spine or joints) may occur years after spondyloarthritis is diagnosed and may be associated with a flare, or be new symptoms related to inflammation in the skin, eye, or gut.
Lastly, patients with spondyloarthritis may also have increased back pain for reasons totally unrelated to the disease. A good example would be an episode of severe acute low back pain in a patient with axial spondyloarthritis (without spinal fusion, and with good mobility in the spine) that started after shoveling snow or moving furniture. In this scenario, the most likely diagnosis is nonspecific low back pain, which is a very common condition in the general population. The pain can be severe and is associated with muscle spasms and limited range of motion. Imaging studies are typically non-diagnostic and therefore not done initially. In most cases, these episodes resolve over the course of days to weeks with appropriate therapy.
Flares are common in spondyloarthritis. The mechanisms underlying these episodic changes in disease activity are not well understood. A return of symptoms back to baseline over the course of days to weeks is characteristic. It is important to distinguish flares from loss of efficacy of medications as well as a number of other conditions that might mimic a flare but require specific and different treatment. I always advise to consult your rheumatologist in case of new and unusual symptoms.
Dr. Ermann is a rheumatologist and researcher, at Brigham & Women’s Hospital. He is also a member of SAA’s Medical and Scientific Advisory Board.
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