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Cachexia is an underappreciated complication of systemic lupus erythematosus, researchers reported.

A total of 56.3% of patients developed the involuntary weight loss accompanied by loss of homeostatic control of protein and energy balance within 5 years of enrollment into a prospective cohort study, according to George Stojan, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.

And although most patients eventually recovered their weight, in 18% the weight loss was permanent, the team reported online in .

Cachexia differs from starvation and malnutrition, conditions that can be promptly reversed by the provision of adequate nutrition. Cachexia is a known feature of many disorders, including cancer, heart failure, and chronic obstructive pulmonary disease, and is associated with functional impairments, loss of quality of life, and mortality. Little is known, however, about the prevalence or impact of cachexia in lupus.

To explore this, Stojan's group analyzed data from 2,452 patients enrolled in the Hopkins Lupus Cohort from 1987 to 2016 and who had their weight recorded at each clinic visit. Mean follow-up was 7.75 years.

Patients' body weight was categorized as:

• Low (body mass index [BMI] below 20)

• Normal (BMI 20-24.9)

• Overweight (25-29.9)

• Obese (30-34.9)

• Severely obese (above 35)

Cachexia was defined as a 5% weight loss in 6 months without starvation relative to average weight in prior visits or a 2% or more weight loss plus a BMI below 20.

Multiple patient and disease characteristics at baseline were associated with the development of cachexia within 5 years. A total of 73.2% of those whose BMI was below 20 met the definition of cachexia at some point, as did 61.1% of those currently using steroids, 59.8% of those who were positive for anti-double stranded DNA antibodies, 66.3% of those with anti-Smith antibodies, 62.8% of those with anti-La antibodies, and 62.8% of those with anti-RNP antibodies.

In addition, cachexia developed in the majority of patients with renal, hematologic, and central nervous system involvement as well as in those with serositis and vasculitis.

The cachexia was classified as intermittent if it resolved, which was the case in 45.6% of patients. Continuous cachexia never resolved and was still present at the end of follow-up, in 18%, while the remainder of patients never developed the condition.

Rate ratios for prior disease manifestations at any time (adjusted for prednisone use) associated with the development of cachexia included:

• Serositis, RR 1.15 (95% CI 1.01-1.30, P=0.03)

• Renal, RR 1.33 (95% CI 1.19-1.49, P<0.001)

• Hematologic, RR 1.26 (95% CI 1.07-1.48, P=0.01)

• Vasculitis, RR 1.28 (95% CI 1.11-1.48, P=0.001)

• Constitutional, RR 1.40 (95% CI 1.25-1.56, P<0.001)

However, when the researchers looked for associations with disease activity in the 3 months preceding the onset of cachexia, they found this to be limited to renal activity (RR 1.3, 95% CI 1.1-1.5, P=0.0048).

Stojan and co-authors then considered the association between intermittent or continuous cachexia and subsequent organ damage, and found that patients whose cachexia was intermittent had elevated risks for developing numerous types of damage including cataracts, retinal changes, optic atrophy, peripheral neuropathy, cerebrovascular accidents, pleural fibrosis, angina, erosive arthritis, osteoporosis, and avascular necrosis.

Patients with continuous cachexia were at increased risk for having an estimated glomerular filtration rate below 50, proteinuria above 3.5 gm/day, and end-stage renal disease.

"It is tempting to draw a parallel between cachexia in systemic lupus erythematosus and cancer cachexia," the researchers noted.

The 56% of patients reported in the study was similar to the 54% prevalence that has been reported in cancer, although cancer patients more often have continuous cachexia, the investigators continued. The high recovery rate in the current study "may be attributable to improved disease activity and decreased systemic inflammation, a concept that remains controversial in cancer-related cachexia."

While the specific mechanisms associated with cachexia in lupus have not been established, pro-inflammatory mediators secreted by tumors also are involved in the pathogenesis of lupus ("tumor-immune system cross-talk") including interleukins 1, 6, 11, and 17, tumor necrosis factor, interferon-γ, and oncostatin M, the authors explained.

"Further studies are needed to elucidate the implications of cachexia in terms of the response to treatment, long-term outcomes, quality of life, as well as its role as a potential cardiovascular risk factor in systemic lupus erythematosus," Stojan and co-authors concluded.

A limitation of the study, they said, was its use of BMI for the analysis, which does not reflect fat versus muscle mass or edema.

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