Older patients demonstrate inflammation, immune activity similar to rheumatic diseases

SAN DIEGO — Older individuals experience reduced immune activity and increased inflammation that often resemble rheumatic and autoimmune diseases, according to data presented at the Congress of Clinical Rheumatology West.

“Older adults are distinct from younger adults,” Devyani Misra, MD, of the department of geriatric medicine at Beth Israel Deaconess Medical Center, in Boston, told attendees. “Their needs are different.”

Misra reminded the audience that aging is a continuous process.

“There is no switch that turns on or off at the age of 65,” she said. “There is no hierarchy of the mechanisms of aging.”

However, Misra added there is a clear outline of what those mechanisms may be. Cellular senescence occurs, as does mitochondrial dysfunction, dysregulated nutrient sensing and loss of proteostasis. Older individuals additionally experience epigenetic alteration, telomere attrition, genomic instability, altered intracellular communication and stem cell exhaustion. Any of these outcomes may happen as an individual ages, either all at once or over time.

According to Misra, rheumatologists should pay particular attention to immunosenescence, or the aging of the immune system. Hemopoietic stem cells are depleted in this process.

“There is a decline in their function and ability to repopulate,” she said.

Innate immunity is impacted, with increased secretion of proinflammatory cytokines from macrophages and fibroblasts, Misra added. Meanwhile, natural killer cells demonstrate lower cytolytic activity.

“Adaptive immunity also is altered, with both B and T lymphocytes being reduced,” Misra said, noting that immunoglobulin diversity is also lost in the aging process.

Another issue Misra highlighted is “inflammaging,” or chronic low-grade systemic inflammation that occurs in older individuals.

“Proinflammatory cytokines are produced,” she said, adding that senescence-associated secretory factor interleukin (IL)-6 is an “important player.”

According to Misra, the consequences of immunosenescence and inflammaging are clear: increased risk for infections and malignancy, along with poor wound healing and reduced response to vaccination.

“These are the same consequences a rheumatologist goes through when prescribing an immune-modulating medication,” she said.

Rheumatologists, then, are often called on to care for these individuals as they age. However, Misra said rheumatology professionals also must manage the late-onset iterations of diseases like rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis.

Late-onset RA generally occurs after age 60 years, according to Misra.

“Late onset disease presents much more acutely than early onset,” she said.

Patients with late-onset RA often demonstrate more systemic symptoms and proximal joint involvement, Misa said. In addition, there is less female preponderance and more comorbidities and disability.

Although treatment guidelines for RA often do not address this patient population, in general, the approach is similar to that for younger adults, according to Misra.

“Start with glucocorticoids but keep them at the lowest dose for the shortest duration,” she said.

Methotrexate remains the “gold standard” conventional synthetic disease-modifying anti-rheumatic drug (DMARD) unless contraindications are noted. Regarding biologics, Misra said tumor necrosis factor (TNF) inhibitors are the first line, with rituximab (Rituxan, Genentech) and abatacept (Orencia, Bristol Myers Squibb) as additional possible options.

Late-onset SLE is often marked by “insidious” onset at age 50 years or older, according to Misra. Although milder disease is often reported in these patients, they can experience more systemic complications.

“It is difficult to assess this because symptoms might be ongoing for a while,” she said.

Meanwhile, OA is the most common joint disease in older adults, according to Misra. Prevalence increases with age. Patients experience significant pain and disability, and the condition is associated with frailty. Unfortunately, no disease-modifying treatments are available for this disease. Patients are encouraged to exercise, with one overarching goal: “Minimize pain and maximize function,” Misra said.

Regarding frailty, Misra encouraged rheumatologists to familiarize themselves with the FRAIL scale, which includes fatigue, resistance, ambulation, illnesses and loss of weight.

“This is a quick and easy way to assess frailty in rheumatic disease,” she said.

Speaking more generally, Misra closed with some pearls for rheumatologists to take back to the clinic. In particular, rheumatologists should remember that patient-centered care is critical when managing older individuals, she said.

“It is the whole patient you are managing, not just the rheumatoid arthritis,” Misra said.

She added that rheumatologists should also consider the so-called “five Ms” — mind, mobility, medications, multi-complexity and matters most.

“Find out what matters most to the patient,” Misra said.

Communication as the centerpiece of this strategy, she added.

“We may think that this 85-year-old woman does not want aggressive treatment,” Misra said. “But maybe she does.”

The final pearl is that most older patients are being managed by several specialists, including geriatricians, physical therapists, cardiologists and social workers.

“We are part of a team,” Misra said.