I was truly stunned Monday when it was announced that Glenn Frey, from the Eagles, had died as a result of complications from his rheumatoid arthritis, ulcerative colitis, and pneumonia.
It was unexpected, shocking, and so wrong that someone so young would die, and from RA. It hit me hard -- a bit worse than Lennon.
The media and most of the lay audience seemed puzzled that "rheumatoid arthritis" or its complications could be the cause of death ... especially in a middle-aged rock icon. The patients, their families, and the populace are not aware that RA can kill. It can hinder what should be a great life. But it is never given the credit it deserves as the potentially devastating disease it can be.
Several publications have noted RA is seldom listed as the cause of death on review of death certificates. A few studies have shown that RA is the underlying cause of death in 18% to 27% of death certificates. A recent study from Brazil showed that the average age at death for RA was 67 years -- the same age as Glenn Frey. The other causes of death include pneumonia, sepsis, renal failure, interstitial lung disease, and heart failure.
While I've always admired his music and talents, I don't know Mr. Frey or any details of his medical conditions. This event begs the question: what can be learned from his unexpected death? Why do RA patients die unexpectedly?
1. RA is deadly. Numerous studies have shown that RA patients live 6-11 fewer years than non-RA controls. This is higher in women, those who are seropositive, and those with active or bad RA. Bad RA is uncontrolled RA, with swollen joints, functional impairments, chronic fatigue, and pain. Bad RA is what rheumatologists worry about, lay awake at night over and it's an important objective of new drugs and research.
2. RA patients are at greater risk of developing comorbidities that contribute to mortal and morbid risks. Lifespan is both pre-ordained and the cumulative effects of lifestyle, consequence, and disease. We know what to expect when someone with a chronic medical condition develops a series of unfortunate additional medical events. Multiple problems portend graver outcomes and, not unexpectedly, the dominoes of life begin to fall.
3. Infection. Pneumonia is the #1 cause of infectious death in RA. Patients are at higher risk for multiple reasons and any individual risk is the result of multiple complex factors. In decreasing order of importance, RA patients develop serious (hospitalizable) infections because of: a) the severity of RA (wherein risk is related to inflammation and debility is the consequence of repeated damage); b) steroid use -- glucocorticoids are acutely wonderful, but they are chronically hazardous. Steroids increase the risk of infections (certainly at doses greater than 5 mg per day), adverse cardiovascular events, and stroke; c) comorbidities, especially chronic lung disease, diabetes, renal, or heart disease; d) breakdown of skin leaving open ulcers or wounds; and e) major surgeries. While drugs are often blamed for an increase in the risk of infection, drugs are only contributory after all of the above have upped the risk of infection. Methotrexate, immunosuppressives, or biologics, in and of themselves, do not significantly increase risk of serious infections.
4. Lymphoma and cancer. Cancer is one of the top three causes of death in RA. These patients have a higher risk of non-Hodgkin's lymphoma, lung cancer, and skin cancer for sure. But they have a lower risk of colon and breast cancer. What is astounding is the data that shows the highest level of disease activity (meaning inflammation) can be associated with a greater than 70-fold increase risk of NHL. This is why patients need to be treated early and aggressively so that years of uncontrolled inflammation will not shift the odds in favor of a future cancer.
5. Cardiovascular death. This includes myocardial infarction, stroke, heart failure, etc. RA patients succumb to CV deaths because of the cumulative detrimental effects of systemic inflammation on the vasculature and myocardium. This can be compounded by chronic NSAIDs (which may cause small but significant increases in hypertension), corticosteroids, weight gain, sedentary lifestyle, etc. There is encouraging strong data that effective suppression of chronic inflammation and disease activity with either methotrexate or TNF inhibitors is associated with prolonged survival -- especially in those who take these drugs for more than 2 years.
6. Chronic lung disease. RA patients have an increased risk of death, but shows this is especially so for lung-related deaths which may outweigh cardiovascular or cancer related deaths. of patients will have chronic interstitial lung disease and chronic lung disease is a major risk factor for infections, pneumonia, and death in RA.
7. Comorbidities. It is not uncommon that RA patients will come down with other autoimmune diseases -- like Sjogren's syndrome, vasculitis, thyroiditis, lupus, etc. It's unclear if this is related to genetics, epigenetics, the microbiome, activated dendritic cells, interferon-α, or netosis unchecked. Ulcerative colitis and RA is a rare association, but ulcerative colitis with a seronegative RA-like arthropathy is not uncommon.
8. Extraarticular manifestations. These include nodules, Sjögren's, vasculitis, rheumatoid lung, rheumatoid vasculitis, inflammatory eye disease (scleritis), Felty's syndrome, amyloidosis, and neuropathy. Collectively, these are associated with more severe disease, seropositivity and destructive, erosive arthritis. Although the prevalence of extraarticular manifestations has dropped significantly in the modern era, with more aggressive interventions, patients with these have a substantially higher mortal risk related to substantially more aggressive disease.
9. Complications of surgery. In the current era of more aggressive therapy, there has been a steady decline in the need for orthopedic surgery and joint replacements. Nonetheless, these are not uncommon in patients with chronic or severe RA. Thankfully the risk of surgically related infection or death is very low, but does occur. have shown that RA patients undergoing arthroplasty have the same low short-term (30 day) mortality risk as osteoarthritis patients (odds ratio 0.94; 95% CI 0.38 to 2.33), but RA was associated with a significantly higher long-term mortality from years 1 to 8 after surgery (hazard ratio 1.22; 95% CI 1.00 to 1.49).
10. Lifestyle. Recent studies have shown environmental factors are more impactful than genetic factors in the onset and progress of RA. Thus, there is clear evidence implicating the following lifestyle factors in the risk and outcomes of RA: smoking, obesity, periodontal disease, and high salt intake. Rheumatologists and patients need to communicate better on these modifiable lifestyle factors that may have long-term if not mortal consequences.
Glenn Frey died when he was 67 years young. 60 is suppose to be the new 40. Hence, Mr. Frey should have had many good years ahead of him, largely because of the advances in treatment and expert care that could have lessened his mortal risks.
The futility in this story is that despite smart care, a vigilant patient and modern medicines, bad things may happen to good people. While I am still encouraged that I can offer great outcomes for most of my patients with rheumatoid arthritis, I am anguished and driven for those with aggressive disease, bad RA and ugly outcomes.
We still have a long way to go in treating this devastating and deadly disease.
, is the director of clinical rheumatology at the Baylor Research Institute and a professor of medicine and rheumatology at Baylor University Medical Center in Dallas. He is the executive editor of . A version of this article first appeared on RheumNow, a news, information and commentary site dedicated to the field of rheumatology. Register to receive their free rheumatology newsletter.
Disclosures
Cush declared he has not received compensation as an advisor or consultant on this subject.