SJIA accounts for about 10 percent of JIA cases, says Jay Mehta, MD, a pediatric rheumatologist and the program director of the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia, and an associate professor of clinical pediatrics at the University of Pennsylvania’s Perelman School of Medicine. JIA affects about 1 in 1,000 children, according to data published in Arthritis Care and Research in June 2019. Juvenile idiopathic arthritis used to be referred to as juvenile rheumatoid arthritis, notes the Arthritis Foundation; that’s no longer the preferred term, though, because JIA is not a childhood version of adult rheumatoid arthritis. RELATED: What Does Arthritis Pain Feel Like? When SJIA develops after age 16, it’s called adult-onset Still’s disease (AOSD). AOSD usually strikes young adults from ages 16 to 35, but it can develop at any age. AOSD is essentially the same disease as SJIA, but it is less common than SJIA for several reasons. “In young children, the immune system is quite naïve and rapidly processing new exposures, but as we get older, our immune systems mature and we are able to recognize more exposures based on previous experience,” says Anjali Sura, MD, a pediatric rheumatologist at SUNY Upstate University Hospital in Syracuse, New York, who has treated both children and young adults. In addition, diseases that affect the innate (general) immune system, including Stills, tend to appear at a younger age than diseases that affect the adaptive (specialized) immune system, such as rheumatoid arthritis, she explains. (The adaptive immune system makes specific antibodies to specific substances, whereas the innate system launches a more general response.) “It’s also likely that there are some genetic and environmental factors involved as well, but we don’t know for sure,” she adds.
What Causes Arthritis in Children and Young People, Such as SJIA and AOSD?
The disease is due to an overactive innate immune system, making it different from most other types of chronic arthritis, which involve the adaptive immune system. SJIA and AOSD are systemic — meaning they affect the entire body — and are also idiopathic, meaning the cause is unknown. Although SJIA and AOSD are diseases of the immune system, they are not considered autoimmune, as are most types of rheumatoid arthritis, lupus, or Sjögren’s syndrome; instead, they’re considered autoinflammatory diseases. No one knows exactly why the innate immune system goes awry, though it may be a response to an infection or have a genetic component. “But not everyone with the genetic markers gets the disease, and not everyone with the disease has the genetic markers,” says Dr. Mehta. Symptoms include:
A daily high fever of 102 degrees F or higher that lasts for a few hours and typically spikes in the afternoon, but can occur anytime. For a patient to be classified as having SJIA, the fever must be present for two or more weeks.A salmon-pink rash that can appear anywhere but often shows up on the limbs and trunk, and comes and goes — often along with a feverJoint pain and swelling in any joint, frequently in the knees, ankles, wrists, and the cervical spine jointsGeneralized muscle pain (myalgia)Lymph node swelling
In many cases the rash and fever occur together, followed by joint pain and inflammation days to months later, says Dr. Sura. But she has also seen cases where the joint symptoms develop first or not at all, particularly if patients are diagnosed early on and begin treatment, thus preventing the progression of the disease. RELATED: Rheumatoid Arthritis Changes You In children, the traditional thought is that about one-third of those with SJIA will have a “one and done” episode: They develop initial symptoms, get diagnosed, start on medication that quells symptoms, and can eventually curtail some or all their meds, says Mehta, adding that the “one and done” scenario is growing thanks to earlier and increased usage of biologic drugs (see below). In Mehta’s experience, and in some recent literature, over one-half of children started on IL-1 blockers quickly go into remission and are able to discontinue medication. The remainder of those with SJIA will have one of two trajectories: They will experience remission with periods of flare-ups or have constant disease activity with inflammation and arthritis. “Many children will outgrow SJIA, but we don’t have great data on this since they transition to adult rheumatologists and we often don’t know the outcomes,” says Mehta. In about 10 percent of SJIA cases (and more rarely in adults), a potentially deadly complication called macrophage activation syndrome (MAS) can develop. In MAS, there is overwhelming systemic inflammation that can affect any organ, including the heart and lungs. Signs of MAS include an unrelenting high fever, enlarged lymph nodes, and an enlarged spleen and liver. Early treatment is vital, as the condition causes death in about 8 percent of cases, notes the American College of Rheumatology. In adults, some older research has suggested that about one-third of those with AOSD will have one episode of fever, rash, or joint pain symptoms (or a combination of two or more of these) that’s short-lived and doesn’t recur, although some experts believe that increased and earlier use of biologic drugs is able to stop the disease progression in its tracks for some young adult sufferers. For the remainder of patients, the disease is likely to be chronic, whether that involves periodic episodes every few weeks, months or years, or continual symptoms. “We really need better and newer data to know exactly how adult patients are doing,” says Sura.
Diagnosing Systemic Juvenile Idiopathic Arthritis (SJIA) and Adult-Onset Still’s Disease (AOSD)
Because there’s no hard-and-fast blood test for SJIA or AOSD, doctors must diagnose the disease based on symptoms, by eliminating other diseases, and by assessing certain biological markers. Blood test results that can indicate SJIA or AOSD include:
High ferritin levels (a protein that stores iron)A high white blood cell count (a high count can indicate an immune disorder or an inflammatory condition)A high erythrocyte sedimentation rateA high C-reactive protein level
(Note that the rheumatoid arthritis factor is usually negative in SJIA and can also be negative for AOSD.) Musculoskelatal X-rays and ultrasound are also used to assess joint damage for diagnosis and remission. Certain conditions are often ruled out before doctors consider SJIA or AOSD. And because the disease shares features with other more common conditions, there can be a delay in diagnosis and treatment. This is especially concerning for SJIA, since untreated SJIA can impair musculoskeletal growth (just like JIA). “Pediatricians will often try antibiotics for what they think are back-to-back viral infections, then they will refer the child to an oncologist, who will rule out cancers, sometimes with a bone marrow biopsy,” says Mehta. It’s often not until the child tests negative for cancers that they are referred to a rheumatologist, causing weeks or months of delay in a diagnosis. “Ideally, a pediatrician will refer a child to a pediatric rheumatologist,” says Mehta. But there are only about 350 pediatric rheumatologists in the country, according to the Arthritis Foundation, which makes the referral process difficult. Oftentimes, rheumatologists who treat adults end up diagnosing SJIA in children. For adults, doctors may first consider a chronic infection or cancer of the immune system, such as lymphoma. Other conditions that a primary care doctor will want to rule out are tuberculosis, bacterial endocarditis, and rheumatic fever. Once these are eliminated, the doctor may refer the patient to a rheumatologist, who will then consider rheumatologic diseases such as AOSD. RELATED: Myths and Facts About Juvenile Idiopathic Arthritis
Treating AOSD and SJIA
The first course of treatment for AOSD is often anti-inflammatory drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, followed by biologics, drugs that are often injected or infused, and which block the activity of inflammatory cytokines, according to the 2021 American College of Rheumatology guidelines to treat JIA. Because there are more medicines approved for SJIA than AOSD, doctors generally treat AOSD with some of the same drugs as SJIA. For oligoarthritis, the guidelines suggest starting patients with NSAIDs, glucocorticosteroids, or both, then prescribing nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs) if pain continues, or treating and monitoring with NSAIDs if it does not. For systemic JIA, the guidelines advise treatment with IL-1 or IL-6 drugs along with either NSAIDs or glucocorticoids, and possibly adding DMARD treatment if pain and symptoms persist. The greatest area of research for both AOSD and SJIA is with the biologic drugs, including Kineret (anakinra), Actemra (tocilizumab), and Ilaris (canakinumab), which block IL-1 and IL-6 (proteins involved in cell signaling) both of which are thought to play a role in the disease. Doctors may also use the IL-1 blocker Arcalyst (rilonacept) or Kevzara (surilumab), a new IL-6 blocker. Some new research is being conducted on IL-18 blockers, since IL-18 cytokines may be elevated in those with MAS, and knowing a person’s IL-18 status could predict who is more likely to develop MAS. Such tests are not yet commercially available. And for those whose disease is resistant to IL-1 and IL-6 blockers, JAK inhibitors (Janus kinase inhibitors) hold promise, according to research published in November 2018 in Current Rheumatology Reports, although large patient trials are still needed to fully understand their efficacy. With SJIA, patients with mild disease are often started on NSAIDs, and they may do well on this treatment alone. For those with moderate or severe disease, biologic drugs are often the first step in order to get symptoms under control. (Steroids may be needed but are used at as low a dose as possible in children because of the concern over their effect on growth.) For children with severe or long-standing SJIA, doctors have recently become aware that lung disease — with symptoms like shortness of breath, rapid breathing, and coughing — may develop, necessitating additional treatment, says Mehta. The reason for the development of lung disease and the optimal treatment for it are still being investigated. Because many of the drugs used to treat SJIA, AOSD, and RA suppress the immune system, patients must be monitored carefully for infections. But all experts agree that risks associated with drug side effects are far, far less worrisome than the risks of not treating the condition aggressively. “Patients are scared of the treatment, but I stress to them that uncontrolled disease is much more risky, especially when you consider the danger of developing MAS,” says Sura. And the outcome is hopeful for those who undergo drug treatment: “Children tend to do really well with treatment, and we can prevent long-term effects of the disease,” says Mehta. In addition to drug therapy, regular physical activity — especially for children, who are still growing and developing — is key to keeping joints flexible and muscles strong (which is important for supporting joints), and in helping to reduce pain. Additional reporting by Cheryl Alkon.
