Missed Red Flags in Rheumatic Care

Fatigue and frailty, two common comorbidities of inflammatory rheumatic diseases, often receive insufficient attention in rheumatologic care settings.

Fatigue significantly reduces quality of life, while frailty is associated with numerous risks and is not limited to older adults, according to Klaus Krüger, MD, head of the St. Bonifatius Rheumatology Practice Center in Munich, Germany.

Speaking at the Rheumatism Update 2025 in Mainz, Germany, Krüger emphasized that frailty is linked to falls, fractures, increased hospitalizations, a nearly threefold higher mortality rate, and frequent infections. Christian Kneitz, MD, a rheumatologist from Schwerin, Germany, confirmed these findings.

“Fatigue is often cited as the second most debilitating manifestation after pain,” Krüger said. Approximately half of individuals with rheumatoid arthritis (RA) complain of fatigue, particularly at the onset of the disease.

Because persistent fatigue causes a high level of suffering and is often refractory to treatment, the European Alliance of Associations for Rheumatology (EULAR) issued specific treatment recommendations in 2024 for managing fatigue in inflammatory rheumatic and musculoskeletal diseases.

Key Recommendations

EULAR guidelines emphasize four critical steps:

1. Regular assessment of fatigue and its associated factors.

2. Physical activity and regular access to physical exercise interventions.

3. Regular access to a structured offer of coping strategies.

4. For persistent or worsening fatigue, inflammatory disease activity status should be evaluated, and treatment should be adjusted accordingly.

“These core recommendations may seem somewhat basic at first glance,” Krüger admitted. However, he noted that stronger evidence is lacking. “For us, these recommendations are important because we can rely on them when dealing with both payers and patients.”

Inflammation Not Always the Cause

The key term is “regularly,” Krüger stressed. Fatigue, like joint pain and swelling, should always be recorded — ideally using tools such as a visual analog scale. This is a standard part of disease monitoring, just like assessing functional status or calculating the Disease Activity Score (DAS).

A Dutch 5-year study involving 1975 patients with RA identified several predictors of persistent fatigue despite adequate antirheumatic therapy:

• A high tender joint count
• A high patient global assessment score
• Surprisingly, monoarticular or oligoarticular onset of disease

Krüger noted he found the latter association puzzling. Fatigue was inversely associated with the swollen joint count and showed no association with the overall DAS. This suggests that persistent fatigue is not always triggered by an inflammatory response.

“Fatigue and inflammatory activity do not necessarily go hand in hand,” Krüger said. Patients often experience pain, but increasing antirheumatic treatment without inflammation is not beneficial. “If fatigue has causes other than disease activity, alternative therapeutic approaches may be necessary,” he added.

Movement, Coping Are Key

Krüger acknowledged that “managing fatigue is a challenging task” and that there are only two therapeutic pillars: Physical exercise and coping strategies. “These are, in fact, the only interventions with proven benefits.” Routine is essential. “These patients should actually be provided with permanent, active exercise interventions.”

Patients can also receive digital support for lifestyle challenges when access to coping strategies is difficult. “There are useful apps,” Krüger noted, “some of which can even be prescribed.” He specifically mentioned a free meditation app from Barmer Krankenkasse, a German health insurance company, which is “particularly suitable for fatigued patients.”

Frailty Worsens Prognosis

Frailty complicates treatment and is “associated with significantly worse outcomes,” Krüger said. Its far-reaching effects are often ignored.

When patients with RA begin treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs and are frail, their risk for severe infections increases by 50%, and their risk for hospitalization rises by 40% compared with non-frail patients.

This was demonstrated in an analysis of insurance data from 57,980 US citizens. “While successful treatment with tumor necrosis factor alpha and Janus kinase inhibitors reduced frailty, even patients receiving treatment still had this increased risk.”

Frailty in Younger Patients

“We typically associate frailty with older patients,” Krüger noted. However, nearly half of older patients with RA are frail, and the disease can also cause frailty in younger individuals.

The US insurance data study also supports this: Although the cohort had a relatively young average age of 48 (all participants were under 65 years), 6% were still classified as frail. “Frailty is not solely a problem for geriatric patients.”

Kneitz concluded from another retrospective cohort study in the United States that it is “Better to be old than frail.” Among 234 individuals with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), those aged 75 years or older had a 2.52-fold higher risk for severe infections than those aged 65-74 years, solely due to age.

However, frailty had a much greater impact. Regardless of age, frailty increased the risk for severe infections by 8.46-fold compared with non-frail individuals.

High Infection Risk

About 37% of those over 75 years and 22% of younger individuals were classified as frail. In both age groups, frailty increased the incidence rate of severe infections — from 0.8 per 100 patient-years (PY) to 38.9 per 100 PY in those aged 65-74 years, and from 12.3 per 100 PY to 61.9 per 100 PY in those aged 75 years or older.

“These are extremely high numbers,” Kneitz emphasized, offering a comparison: “In clinical trials, biologic therapies typically result in three to four severe infections per 100 PY.”

For Kneitz, the conclusion is clear: “Frailty significantly increases the risk of severe infections.” This is particularly true for patients with AAV and lung involvement. In a Japanese cohort study of 115 patients with microscopic polyangiitis and interstitial lung disease, respiratory infections accounted for 69% of the deaths.

“These are patients we need to monitor very closely,” Kneitz said, describing frailty in this context as an “extreme problem.” He also cautioned against the undertreatment of patients. “The presence of frailty in older adults is not a reason to withhold potentially effective treatment for ANCA-associated vasculitis.” On the contrary: “If we don’t treat these patients, infections will become an even more severe.”

Quick Frailty Test

Various tools are available to assess frailty. Krüger highlighted the chair sit-to-stand test as a practical option that takes less than a minute. “This test allows us to quickly identify at-risk patients.” The test requires patients to cross their arms over their chest and rise from a chair without armrests five times as fast as possible. Krüger noted that normal time ranges from 10.8 to 12.8 seconds.

This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.