Stress triggers disease flares in patients with vasculitis

This is the first study to suggest that mental health is a risk factor in patients with vasculitis, a group of autoimmune disorders characterized by the inflammatory destruction of blood vessels. The study, in a form of the disease known as Wegener's granulomatosis (WG), will be presented on Nov. 8 at the American College of Rheumatology's annual meeting.

"When this disease flares, people can be really sick. It often affects the lungs, kidneys, sinuses and nerves. It can cause fevers and rashes. People can die from this illness. It is a very robust, active, inflammatory disease when it is active," said Robert Spiera, M.D., director of the Vasculitis and Scleroderma Program at HSS, who led the study. "When patients are in remission, however, they can do very, very well."

He says that doctors caring for patients with this disease should be attentive to their psychological health. "This study points out that mental health should be part of your medical assessment," said Dr. Spiera. "You should pay attention to the patient's mental well being and be more aggressive about intervening if a patient is in a bad place. Make sure that patients take it seriously."

Prior to this report, a few small studies had suggested that psychological stress can trigger flares of lupus, another autoimmune disease, and doctors have observed that WG patients often say that stress in their lives, caused by perhaps a death of someone close or losing a job, made their disease flare. To investigate this anecdotal evidence in a more quantifiable way, researchers at HSS conducted a retrospective analysis of data from the Wegener's Granulomatosis Etanercept Trial (WGET). The primary objective of this randomized, placebo-controlled clinical trial was to evaluate the safety and efficacy of using etanercept (Enbrel; Immunex Corporation) to get patients with WG into remission and maintain that remission.

All patients in this multicenter trial had active disease at the beginning of the study and most patients went into remission. Checkups occurred every three months. "We assessed their disease activity at defined time intervals, in terms of how active their vasculitis was or whether they were in remission, and we also collected information at every visit regarding the patient's physical and mental health," Dr. Spiera said. Investigators measured disease activity using the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis, a validated tool. At every visit, patients also filled out the Short Form 36 Health Survey, which includes a physical and mental component. Summary scores for each component are measured on a scale of 0 to 100, with 100 being the healthiest.

For their retrospective analysis of WGET, HSS investigators reviewed records of all patients who had a sustained remission of at least six months (143 patients). They then reviewed data from all checkups after the time of sustained remission to assess the relationship between flare status and the physical and mental health scores from the previous visit. They found that patients were 19 percent more likely to experience a disease flare if they had a five point lower mental health score (P<0.01) at the checkup immediately prior to the flare. The physical component score did not predict an activation of the disease.

"If you looked at patients who were in remission for six months or longer and assessed their mental health as captured by this mental health score, those with a lower mental health score at a given point in time would be more likely to be flaring at the next visit, within three months," Dr. Spiera said. "This is the first time that as an independent variable, stress seemed to predict a greater likelihood of flaring."

The study suggests that doctors need to be attentive to a patient's psychological state and be proactive about interventions to help them manage stress. "There are a lot of things that can be done proactively in stress management on the patient's side outside of seeing a psychiatrist," Dr. Spiera said. For example, exercise and yoga have been shown to be effective stress relievers.

The HSS researchers next hope to prospectively examine the association between psychological state and flares in upcoming trials of vasculitis and other autoimmune diseases. Some investigators have hypothesized that stress-related hormones lead to immune dysregulation, but research is needed to tease out the mechanisms.

"Going forward, we can even think of trials where you would take patients who have declined in their mental component score and randomize half of them to receive some sort of stress management program and half of them not to receive it, to see if it changes their outcomes," Dr. Spiera said.

Wegener's granulomatosis was recently renamed granulomatosis with polyangiitis. The rare disease, in which inflamed blood vessels interfere with blood circulation, mainly affects vessels in the nose, sinuses, ears, lungs and kidneys, although other areas may be involved. It is most common in middle-aged adults.

Other authors of the study are Morgana Davids and Huong Do at HSS; Gunnar Tomasson, M.D., Boston University School of Medicine; John Davis Jr., M.D., MPH, Genentech; Gary Hoffman, M.D., Cleveland Clinic; W. Joseph McCune, M.D., University of Michigan; Ulrich Specks, M.D., Mayo Clinic; E. William St Clair, M.D., Duke University Medical Center; John Stone, M.D., MPH, Massachusetts General Hospital; and Peter Merkel, M.D., Ph.D., Boston University.