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Study Shines Light on Rare, Underdiagnosed Autoinflammatory Disease

A new study by researchers from Hospital for Special Surgery shines a light on Adult Onset Still’s Disease (AOSD), a rare autoinflammatory disorder that is underdiagnosed in the United States, and identifies risk factors that predispose afflicted patients to worse outcomes. The study, which appears online ahead of print in the journal Seminars in Arthritis and Rheumatism (April 25; pii: S0049-0172(19)30123-4), found that Asians were six times more likely to die from the disease and that patients with a particular complication called Disseminated Intravascular Coagulation were 30 times more likely to die in the hospital from the disease.

“There is very little known about Still’s disease,” said lead author Bella Mehta, MBBS, MD, MS, rheumatologist at Hospital for Special Surgery, in New York City. “When clinicians see a patient who is Asian with intermittent fevers and rashes, try to think of Still’s disease. If you don’t think about it, you are never going to diagnose it. Still’s is a rare, heterogenous disease, so every patient presents slightly differently, and it is difficult to diagnose. It has to be on your radar, if you are ever going to diagnose it.”

Adult Onset Still’s Disease is characterized by intermittent spiking high fevers, arthritis or arthralgia, and an evanescent (lasting less than 24 hours) maculopapular skin rash. AOSD remains a mystery on many fronts. While both genetics and infectious triggers have been suggested to play a role, the etiology of AOSD remains unknown. The disease is complex and associated with high morbidity and mortality. Complications of the disease including Macrophage Activation Syndrome, Disseminated Intravascular Coagulation (DIC) and Thrombotic Thrombocytopenic Purpura are life threatening.

AOSD is estimated to impact 0.16-0.4 per 100,000 persons and little epidemiological data on the disorder exists. Most available data comes from single centers or a single geographic region. There are no large-scale studies in the United States describing the demographics, complications or mortality in patients with the disease.

To help fill the knowledge gap, researchers led by Dr. Mehta set out to describe the demographics of U.S. hospitalized patients with AOSD, the morbidity and complications leading to mortality, and the risk factors associated with adverse outcomes in patients. The investigators used retrospective data from the 2009-2013 Nationwide Inpatient Sample (NIS) database, the largest publicly available all-payer inpatient care dataset in the United States. This database contains discharge data from approximately 20% of nonfederal, short-term, general and other specialty hospitals in the United States. Using NIS, the researchers identified all patients 18 years and older with a primary diagnosis of AOSD from 2009 to 2013. To minimize misclassification bias, they excluded patients with a concurrent diagnosis of rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, polymyalgia rheumatica, ankylosing spondylitis, inflammatory myopathies, or systemic sclerosis.

Dr. Mehta and colleagues identified 5,820 patients admitted for AOSD in hospitals across the United States between 2009 and 2013. The average age was 53.6 years and 65.6% were females. The majority of patients, 56%, were white, 3% were Asian, and 31% were African American, Hispanic or other. Race was not identified for 10% of patients. Roughly 40% of patients were hospitalized in urban teaching hospitals, and 42% were admitted in large volume hospitals. In the sample, 1.7% were diagnosed with Macrophage Activation Syndrome, 1.1% had Disseminated Intravascular Coagulation, and 0.4% had Thrombotic Thrombocytopenic Purpura.

The mortality rate was 2.6% in hospitalized AOSD patients, and the mean age of these patients was 62.4. Asians were 6.39 times more likely to die in the hospital compared with whites. “The finding that Asians were much more likely to die was important; the disease is more prevalent in Southeast Asia,” said Dr. Mehta. “Asians seem to have a different intensity of the disease.”

Dr. Mehta said clinicians need to be thinking more about Still’s. “Sometimes it takes months and months for a patient to even get to a rheumatologist with suspected Still’s disease,” said Dr. Mehta. “More awareness of the disease would lead to more diagnosis.”

The researchers also found that older age increased mortality and for every increase in the number of medical conditions, the odds of in-hospital mortality increased by 20%. Patients who developed Disseminated Intravascular Coagulation were 30 times more likely to die in the hospital.

“Older age increases mortality for most other diseases too, so that was not an uncommon finding, but if you have an older person with a lot of comorbid conditions with Still’s disease, you need to be much more vigilant,” said Dr. Mehta. She said that DIC should be a red flag for clinicians. “Patients with Still’s disease who have Disseminated Intravascular Coagulation have really bad outcomes, so watch for signs and symptoms of this, adjust the expectations of the patient and family, and start treating aggressively at the first sign of DIC,” said Dr. Mehta.

While prospective studies of Still’s would be ideal to get a firm grasp on the disease, said Dr. Mehta, the new study, with one of the largest cohorts of Still’s disease patients, is the best data available so far. “Before this study, we did not have any idea of Still’s disease patients in the U.S. and predictors of worse outcomes,” she said. “Now, at least in the U.S., we know that Asians have worse outcomes and so do patients who have Disseminated Intravascular Coagulation.”

About HSS | Hospital for Special Surgery

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 14th consecutive year), No. 2 in rheumatology by U.S. News & World Report (2023-2024), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2023-2024). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fourth consecutive year (2023). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.